Article The Mechanism of Triacetyl Andrographolide in Inhibiting Proliferation of Pulmonary Artery Smooth Muscle Cells Zhe Wang 1,#, Yi-Xuan Zhang 2,#, Jun-Zhuo Shi 1,#, Chen-Chen Wang 1, Meng-Qi Zhang 1, Yi Yan 3, Yan-Ran Wang 1, Lu-Ling Zhao 1, Jie-Jian Kou 4, Qing-Hui Zhao 5, Xin-Mei Xie 1, Yang-Yang He 1,2, Jun-Ke Song 6,*, Guang Han 1,7,*, and Xiao-Bin Pang 1,2,* 1 School of Pharmacy, Henan University, Kaifeng 475004, China 2 Department of Anesthesiology, Huaihe Hospital of Henan University, Kaifeng 475004, China 3 Heart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200217, China 4 Department of Pharmacy, Huaihe Hospital of Henan University, Kaifeng 475004, China 5 Institute of Physical Culture, Huanghuai University, Zhumadian 463000, China 6 Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China 7 Henan Province Engineering Research Center of High Value Utilization to Natural Medical Resource in Yellow River Basin, Kaifeng 475004, China. * Correspondence: smilejunke@imm.ac.cn (Jun-Ke Song); hang@henu.edu.cn ( Guang Han); pxb@vip.henu.edu.cn ( Xiao-Bin Pang) Received: 17 April 2023 Accepted: 27 July 2023 Abstract: This study examines the impact of triacetyl-diacyllactone (ADA) on the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) and elucidates its underlying mechanism. PASMCs derived from SD rats were cultured in vitro and randomly divided into four groups: control group, administration group, model group, and model administration group. The appropriate concentration of ADA for intervention was determined using the MTT assay. The proliferation ability of PASMCs in each group was assessed using the EdU assay. The migration ability of PASMCs in each group was evaluated using the Scratch wound healing assay and Transwell assay. Western blot analysis was performed to determine the protein expression levels of BMPR2, PCNA, and TGF-β1, as well as the phosphorylation levels of SMAD1 and SMAD2/3 in PASMCs from each group. Results show that at a concentration of 5 µmol/L, ADA did not impact the cell activity of PASMCs and instead exerted inhibitory effects on both the proliferation and migration of PASMCs induced by PDGF-BB. PDGF-BB was found to upregulate the expression levels of PCNA and TGF-β1, while downregulating the expression of BMPR2. Furthermore, PDGF-BB led to enhanced protein phosphorylation of SMAD1 and SMAD2/3. However, following ADA intervention, the expression levels of PCNA and TGF-β1 decreased, while the expression of BMPR2 increased. Additionally, protein phosphorylation of SMAD1 and SMAD2/3 decreased. Therefore, ADA can hinder the proliferation and migration of PASMCs induced by PDGF-BB, as well as suppress the up
{"title":"The Mechanism of Triacetyl Andrographolide in Inhibiting Proliferation of Pulmonary Artery Smooth Muscle Cells","authors":"Zhe Wang, Yi-Xuan Zhang, Jun-Zhuo Shi, Chen-Chen Wang, Meng-Qi Zhang, Yi Yan, Yan-Ran Wang, Lu-Ling Zhao, Jie-Jian Kou, Qing-Hui Zhao, Xin-Mei Xie, Yang-Yang He, Jun-Ke Song, Guang Han, Xiao-Bin Pang","doi":"10.53941/ijddp.2023.100009","DOIUrl":"https://doi.org/10.53941/ijddp.2023.100009","url":null,"abstract":"Article The Mechanism of Triacetyl Andrographolide in Inhibiting Proliferation of Pulmonary Artery Smooth Muscle Cells Zhe Wang 1,#, Yi-Xuan Zhang 2,#, Jun-Zhuo Shi 1,#, Chen-Chen Wang 1, Meng-Qi Zhang 1, Yi Yan 3, Yan-Ran Wang 1, Lu-Ling Zhao 1, Jie-Jian Kou 4, Qing-Hui Zhao 5, Xin-Mei Xie 1, Yang-Yang He 1,2, Jun-Ke Song 6,*, Guang Han 1,7,*, and Xiao-Bin Pang 1,2,* 1 School of Pharmacy, Henan University, Kaifeng 475004, China 2 Department of Anesthesiology, Huaihe Hospital of Henan University, Kaifeng 475004, China 3 Heart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200217, China 4 Department of Pharmacy, Huaihe Hospital of Henan University, Kaifeng 475004, China 5 Institute of Physical Culture, Huanghuai University, Zhumadian 463000, China 6 Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China 7 Henan Province Engineering Research Center of High Value Utilization to Natural Medical Resource in Yellow River Basin, Kaifeng 475004, China. * Correspondence: smilejunke@imm.ac.cn (Jun-Ke Song); hang@henu.edu.cn ( Guang Han); pxb@vip.henu.edu.cn ( Xiao-Bin Pang) Received: 17 April 2023 Accepted: 27 July 2023 Abstract: This study examines the impact of triacetyl-diacyllactone (ADA) on the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) and elucidates its underlying mechanism. PASMCs derived from SD rats were cultured in vitro and randomly divided into four groups: control group, administration group, model group, and model administration group. The appropriate concentration of ADA for intervention was determined using the MTT assay. The proliferation ability of PASMCs in each group was assessed using the EdU assay. The migration ability of PASMCs in each group was evaluated using the Scratch wound healing assay and Transwell assay. Western blot analysis was performed to determine the protein expression levels of BMPR2, PCNA, and TGF-β1, as well as the phosphorylation levels of SMAD1 and SMAD2/3 in PASMCs from each group. Results show that at a concentration of 5 µmol/L, ADA did not impact the cell activity of PASMCs and instead exerted inhibitory effects on both the proliferation and migration of PASMCs induced by PDGF-BB. PDGF-BB was found to upregulate the expression levels of PCNA and TGF-β1, while downregulating the expression of BMPR2. Furthermore, PDGF-BB led to enhanced protein phosphorylation of SMAD1 and SMAD2/3. However, following ADA intervention, the expression levels of PCNA and TGF-β1 decreased, while the expression of BMPR2 increased. Additionally, protein phosphorylation of SMAD1 and SMAD2/3 decreased. Therefore, ADA can hinder the proliferation and migration of PASMCs induced by PDGF-BB, as well as suppress the up","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"47 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135343352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-28DOI: 10.53941/ijddp.2023.100008
Weiye Zhao, Hao Xu, Hanwen Zhang, Bin Yan
Review The Role of Macrophages in Orthodontic Tooth Movement: A Review Weiye Zhao 1,2,3, Hao Xu 1,2,3, Hanwen Zhang 4,5,*, and Bin Yan 1,2,3,* 1 Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China 2 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210008, China 3 Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing 210008, China 4 School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210008, China 5 Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 210008, China * Correspondence: hanwenzhang@njmu.edu.cn(Hanwen Zhang); byan@njmu.edu.cn (Bin Yan); Received: 24 April 2023 Accepted: 12 June 2023 Abstract: Orthodontic tooth movement (OTM) is facilitated by the induction of mechanical force, which triggers a sterile inflammatory response in the periodontal tissues. This response, in turn, coordinates the processes of bone resorption and formation. Through an extensive review of the existing literature on the biology of OTM, it becomes evident that macrophages play a pivotal role in all stages of the process. Furthermore, researchers have identified various emerging drugs and biological agents that target the behavior of macrophages, aiming to regulate and control the rate of OTM. To date, most studies have primarily focused on investigating the effects of anti-inflammatory drugs on the rate of OTM and elucidating their specific mechanisms. However, there is a notable absence of reports specifically addressing drugs capable of accelerating tooth movement. Nonetheless, in other fields, such as the promotion of fracture healing, techniques for modulating macrophage function using bio-scaffolds or sustained-release formulations loaded with cytokines or drugs have demonstrated significant advancements. Thus, these techniques hold promise as important avenues for future research and development, exploring the potential of macrophages in regulating the rate of OTM.
{"title":"The Role of Macrophages in Orthodontic Tooth Movement: A Review","authors":"Weiye Zhao, Hao Xu, Hanwen Zhang, Bin Yan","doi":"10.53941/ijddp.2023.100008","DOIUrl":"https://doi.org/10.53941/ijddp.2023.100008","url":null,"abstract":"Review The Role of Macrophages in Orthodontic Tooth Movement: A Review Weiye Zhao 1,2,3, Hao Xu 1,2,3, Hanwen Zhang 4,5,*, and Bin Yan 1,2,3,* 1 Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China 2 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210008, China 3 Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing 210008, China 4 School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210008, China 5 Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 210008, China * Correspondence: hanwenzhang@njmu.edu.cn(Hanwen Zhang); byan@njmu.edu.cn (Bin Yan); Received: 24 April 2023 Accepted: 12 June 2023 Abstract: Orthodontic tooth movement (OTM) is facilitated by the induction of mechanical force, which triggers a sterile inflammatory response in the periodontal tissues. This response, in turn, coordinates the processes of bone resorption and formation. Through an extensive review of the existing literature on the biology of OTM, it becomes evident that macrophages play a pivotal role in all stages of the process. Furthermore, researchers have identified various emerging drugs and biological agents that target the behavior of macrophages, aiming to regulate and control the rate of OTM. To date, most studies have primarily focused on investigating the effects of anti-inflammatory drugs on the rate of OTM and elucidating their specific mechanisms. However, there is a notable absence of reports specifically addressing drugs capable of accelerating tooth movement. Nonetheless, in other fields, such as the promotion of fracture healing, techniques for modulating macrophage function using bio-scaffolds or sustained-release formulations loaded with cytokines or drugs have demonstrated significant advancements. Thus, these techniques hold promise as important avenues for future research and development, exploring the potential of macrophages in regulating the rate of OTM.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"225 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135344557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-28DOI: 10.53941/ijddp.2023.100007
Jia Wei, Qiang Yang, Lin Lin, Canzhan Zhu, Jin Wei
Review Quantitative Risk Stratification Models for Coronary Heart Disease in Primary and Secondary Prevention Wei Jia#, Yang Qiang #, lin Lin , Canzhan Zhu , and Wei Jin * Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China. * Correspondence: weijin@mail.xjtu.edu.cn；Tel: +86 13572140118 # Jia Wei and Qiang Yang are equally contributed to the manuscript. Received: 30 April 2023 Accepted: 13 June 2023 Abstract: Coronary heart disease (CHD) is the most prevalent non-communicable disease globally and has high morbidity, mortality and healthcare cost. Thus early and precise risk stratification is an important issue in the detection, diagnosis and therapy for CHD. There are a number of primary screening tools and risk scores involving CHD risk factors for cardiovascular disease worldwide, such as Framingham Risk Score, World Health Organization/International Society of Hypertension and Cardiovascular disease (CVD) risk prediction charts (RiskWHO), American College of Cardiology/American Heart Association (ACC/AHA) pooled cohort equations (RiskACC/AHA), ADAPT Protocol for Cardiac Event Risk. Those models calculate CHD risk based on CHD risk factors, including age, gender, hypertension, and diabetes mellitus. This review will summarize the risk stratification models of CHD and related clinical evidence. It will also include a thorough analysis of the current risk stratification models and offer some advice for future risk stratification model development.
{"title":"Quantitative Risk Stratification Models for Coronary Heart Disease in Primary and Secondary Prevention","authors":"Jia Wei, Qiang Yang, Lin Lin, Canzhan Zhu, Jin Wei","doi":"10.53941/ijddp.2023.100007","DOIUrl":"https://doi.org/10.53941/ijddp.2023.100007","url":null,"abstract":"Review Quantitative Risk Stratification Models for Coronary Heart Disease in Primary and Secondary Prevention Wei Jia#, Yang Qiang #, lin Lin , Canzhan Zhu , and Wei Jin * Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China. * Correspondence: weijin@mail.xjtu.edu.cn；Tel: +86 13572140118 # Jia Wei and Qiang Yang are equally contributed to the manuscript. Received: 30 April 2023 Accepted: 13 June 2023 Abstract: Coronary heart disease (CHD) is the most prevalent non-communicable disease globally and has high morbidity, mortality and healthcare cost. Thus early and precise risk stratification is an important issue in the detection, diagnosis and therapy for CHD. There are a number of primary screening tools and risk scores involving CHD risk factors for cardiovascular disease worldwide, such as Framingham Risk Score, World Health Organization/International Society of Hypertension and Cardiovascular disease (CVD) risk prediction charts (RiskWHO), American College of Cardiology/American Heart Association (ACC/AHA) pooled cohort equations (RiskACC/AHA), ADAPT Protocol for Cardiac Event Risk. Those models calculate CHD risk based on CHD risk factors, including age, gender, hypertension, and diabetes mellitus. This review will summarize the risk stratification models of CHD and related clinical evidence. It will also include a thorough analysis of the current risk stratification models and offer some advice for future risk stratification model development.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"63 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135343356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-28DOI: 10.53941/ijddp.2023.100010
Xinyu Zhang, Hongyuan Zhang
Article Effect of Glucagon-like Peptide-1 Receptor Agonist on Cardiac Structure and Function in Patients with Heart Failure: A Systematic Review and Meta-analysis Xinyu Zhang 1, and Hongyuan Zhang 2, * 1 Division of Bioscience, University College London, London, UK 2 Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK * Correspondence: hongyuan.zhang-3@postgrad.manchester.ac.uk Received: 23 May 2023 Accepted: 8 August 2023 Abstract: Recent clinical trials have shown that glucagon-like peptide-1 receptor agonists (GLP-1RAs) yield positive effects on composite cardiovascular endpoints, rendering them potentially promising therapeutic agents for heart failure (HF). This study analysed the effect of GLP-1RAs on cardiac structure and function in HF patients. MethodsA comprehensive search was conducted across PubMed, Cochrane Library, Ovid Embase, Ovid Medline, and Web of Science databases, spanning from inception to August 1, 2022, to identify randomised controlled trials (RCTs) comparing alterations in cardiac structure and function in HF patients receiving GLP-1RAs or placebo. Cardiac structures were assessed through left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and left ventricular mass (LVM). Systolic function was evaluated using left ventricular ejection fraction (LVEF), stroke volume (SV), and global longitudinal strain (GLS). Diastolic function was assessed via the early to late diastolic filling velocity ratio (E/A ratio) and the early transmitral filling velocity to early diastolic mitral annular velocity ratio (E/e ratio). The I2 statistic was used to test heterogeneity. Pooled relative risks were calculated using random-effects models. Potential publication bias was assessed using the Cochrane Risk of Bias 2 tool. ResultsA total of 1,417 patients from 16 randomised placebo-controlled trials were enrolled in this meta-analysis. Among all HF patients, GLP-1RAs demonstrated improvement in diastolic function as indicated by E/A (MD = -0.15; 95% CI: -0.21 to -0.09; P < 0.00001; I2 = 43%) and E/e’ (MD = -0.82; 95% CI: -1.53 to -0.11; P = 0.02; I2= 62%). However, GLP-1RAs did not exhibit any improvement in cardiac structure and systolic function parameters for HF patients. ConclusionGLP-1RAs demonstrated potential for improving diastolic function in HF patients, but did not show any impact on systolic function and cardiac structure. Therefore, the application of GLP-1RAs should be based on the specific HF type and accompanying comorbidities.
{"title":"Effect of Glucagon-like Peptide-1 Receptor Agonist on Cardiac Structure and Function in Patients with Heart Failure: A Systematic Review and Meta-analysis","authors":"Xinyu Zhang, Hongyuan Zhang","doi":"10.53941/ijddp.2023.100010","DOIUrl":"https://doi.org/10.53941/ijddp.2023.100010","url":null,"abstract":"Article Effect of Glucagon-like Peptide-1 Receptor Agonist on Cardiac Structure and Function in Patients with Heart Failure: A Systematic Review and Meta-analysis Xinyu Zhang 1, and Hongyuan Zhang 2, * 1 Division of Bioscience, University College London, London, UK 2 Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK * Correspondence: hongyuan.zhang-3@postgrad.manchester.ac.uk Received: 23 May 2023 Accepted: 8 August 2023 Abstract: Recent clinical trials have shown that glucagon-like peptide-1 receptor agonists (GLP-1RAs) yield positive effects on composite cardiovascular endpoints, rendering them potentially promising therapeutic agents for heart failure (HF). This study analysed the effect of GLP-1RAs on cardiac structure and function in HF patients. MethodsA comprehensive search was conducted across PubMed, Cochrane Library, Ovid Embase, Ovid Medline, and Web of Science databases, spanning from inception to August 1, 2022, to identify randomised controlled trials (RCTs) comparing alterations in cardiac structure and function in HF patients receiving GLP-1RAs or placebo. Cardiac structures were assessed through left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and left ventricular mass (LVM). Systolic function was evaluated using left ventricular ejection fraction (LVEF), stroke volume (SV), and global longitudinal strain (GLS). Diastolic function was assessed via the early to late diastolic filling velocity ratio (E/A ratio) and the early transmitral filling velocity to early diastolic mitral annular velocity ratio (E/e ratio). The I2 statistic was used to test heterogeneity. Pooled relative risks were calculated using random-effects models. Potential publication bias was assessed using the Cochrane Risk of Bias 2 tool. ResultsA total of 1,417 patients from 16 randomised placebo-controlled trials were enrolled in this meta-analysis. Among all HF patients, GLP-1RAs demonstrated improvement in diastolic function as indicated by E/A (MD = -0.15; 95% CI: -0.21 to -0.09; P < 0.00001; I2 = 43%) and E/e’ (MD = -0.82; 95% CI: -1.53 to -0.11; P = 0.02; I2= 62%). However, GLP-1RAs did not exhibit any improvement in cardiac structure and systolic function parameters for HF patients. ConclusionGLP-1RAs demonstrated potential for improving diastolic function in HF patients, but did not show any impact on systolic function and cardiac structure. Therefore, the application of GLP-1RAs should be based on the specific HF type and accompanying comorbidities.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135344563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-27DOI: 10.53941/ijddp.2023.100002
Haishan Xu, J. Duan, J. Tao, Wen Wang, Yunqing Wu, S. Dai, Jun Ren
Article Oxidized LDL Regulates Endothelin-1 and Oxidative Stress in Vascular Endothelial Cells: Role of Extracellular Regulated Kinase1/2 (ERK1/2) Haishan Xu 1,#, Jinhong Duan 1,#, Jun Tao 2, Wen Wang 3, Yunqing Wu 1,^, Shunling Dai 1,*, and Jun Ren 4,5, 1 Faculty of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005 China 2 Department of Cardiovascular Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510000 China 3 Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China 4 Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai 200032, China 5 National Clinical Research Center for Interventional Medicine, Shanghai 200032, China # These two authors contributed equally to this work ^ Deceased * Correspondence: daishunling@aliyun.com (Shunling Dai); corresponding author:jren_aldh2@outlook.com (Jun Ren) Abstract: It is perceived that oxidized low density lipoprotein (oxLDL) perturbs endothelial function and fosters endothelin-1 (ET-1) secretion although the underlying mechanism remains elusive. This study was designed to decipher potential mechanisms underscoring oxLDL-evoked regulation of ET-1 and signaling pathways involved in endothelial cells. ET-1 mRNA expression, secretion and promoter function were determined using RT-PCR, enzyme immunometric and luciferase assays, respectively. GO and GSEA bioinformatics analyses depicted differentially expressed genes (DEGs) mainly associated with cell proliferation, cell division, cellular structure, energy supply, and apoptosis in oxLDL-challenged endothelial cells. Incubation of oxLDL overtly increased ROS production, apoptosis, mRNA level, secretion and promoter activity of ET-1 in human umbilical vein endothelial cells (HUVECs), the effects were mitigated by N-Acetyl Cysteine (NAC). Moreover, oxLDL challenge evoked phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) in HUVECs, the effect was reversed by NAC and MEK inhibitor PD98059. NAC and PD98059 nullified oxLDL- induced rises in mRNA expression, secretion and promoter activity of ET-1. Truncation of 5’-flanking sequence of ET-1 (–566 bpLuc to –250 bpLuc) displayed elevated luciferase activity with 24-h oxLDL incubation. Fusion plasmid from –233 and –185 bp Luc drastically dampened luciferase activity in basal and oxLDL-challenged HUVECs. Transfection of reporter construct –250 bp Luc with a 2 bp mutation at AP-1 locus, removed basal and oxLDL- evoked rises in ET-1 promoter activity. Collectively, our findings support that oxLDL evoked activation of ERK1/2 signaling likely through ROS production, en route to upregulation of endothelial transcriptional factor AP-1, resulting in expression and secretion of ET-1.
{"title":"Oxidized LDL Regulates Endothelin-1 and Oxidative Stress in Vascular Endothelial Cells: Role of Extracellular Regulated Kinase1/2 (ERK1/2)","authors":"Haishan Xu, J. Duan, J. Tao, Wen Wang, Yunqing Wu, S. Dai, Jun Ren","doi":"10.53941/ijddp.2023.100002","DOIUrl":"https://doi.org/10.53941/ijddp.2023.100002","url":null,"abstract":"Article Oxidized LDL Regulates Endothelin-1 and Oxidative Stress in Vascular Endothelial Cells: Role of Extracellular Regulated Kinase1/2 (ERK1/2) Haishan Xu 1,#, Jinhong Duan 1,#, Jun Tao 2, Wen Wang 3, Yunqing Wu 1,^, Shunling Dai 1,*, and Jun Ren 4,5, 1 Faculty of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005 China 2 Department of Cardiovascular Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510000 China 3 Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China 4 Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai 200032, China 5 National Clinical Research Center for Interventional Medicine, Shanghai 200032, China # These two authors contributed equally to this work ^ Deceased * Correspondence: daishunling@aliyun.com (Shunling Dai); corresponding author:jren_aldh2@outlook.com (Jun Ren) Abstract: It is perceived that oxidized low density lipoprotein (oxLDL) perturbs endothelial function and fosters endothelin-1 (ET-1) secretion although the underlying mechanism remains elusive. This study was designed to decipher potential mechanisms underscoring oxLDL-evoked regulation of ET-1 and signaling pathways involved in endothelial cells. ET-1 mRNA expression, secretion and promoter function were determined using RT-PCR, enzyme immunometric and luciferase assays, respectively. GO and GSEA bioinformatics analyses depicted differentially expressed genes (DEGs) mainly associated with cell proliferation, cell division, cellular structure, energy supply, and apoptosis in oxLDL-challenged endothelial cells. Incubation of oxLDL overtly increased ROS production, apoptosis, mRNA level, secretion and promoter activity of ET-1 in human umbilical vein endothelial cells (HUVECs), the effects were mitigated by N-Acetyl Cysteine (NAC). Moreover, oxLDL challenge evoked phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) in HUVECs, the effect was reversed by NAC and MEK inhibitor PD98059. NAC and PD98059 nullified oxLDL- induced rises in mRNA expression, secretion and promoter activity of ET-1. Truncation of 5’-flanking sequence of ET-1 (–566 bpLuc to –250 bpLuc) displayed elevated luciferase activity with 24-h oxLDL incubation. Fusion plasmid from –233 and –185 bp Luc drastically dampened luciferase activity in basal and oxLDL-challenged HUVECs. Transfection of reporter construct –250 bp Luc with a 2 bp mutation at AP-1 locus, removed basal and oxLDL- evoked rises in ET-1 promoter activity. Collectively, our findings support that oxLDL evoked activation of ERK1/2 signaling likely through ROS production, en route to upregulation of endothelial transcriptional factor AP-1, resulting in expression and secretion of ET-1.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81139244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-27DOI: 10.53941/ijddp.2023.100005
Jiayu Guo, Yan Wang, Haihai Liang, Baofeng Yang
Review Small Leucine Rich Proteoglycan in Fibrotic Diseases: New Frenemies? Jiayu Guo 1,2, Yan Wang 1,2, Haihai Liang 1,2,3,*, and Baofeng Yang 1,2,3,* 1 Department of Pharmacology (National Key Laboratory of Frigid Zone Cardiovascular Diseases), College of Pharmacy, Harbin Medical University, Harbin 150081, China 2 Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin 150081, China 3 Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2019RU070), Chinese Academy of Medical Sciences, Harbin 150081, China * Correspondence: lianghaihai@ems.hrbmu.edu.cn (H.H.L),; yangbf@ems.hrbmu.edu.cn (B.F.Y) Received: 27 April 2023 Accepted: 2 June 2023 Abstract: The human body is a complex organism with self-regulating ability and can cope with external pressures and challenges. To protect the body from damage during exercise or confrontations, beneath the human epidermal layer, the human body has evolved a coverall gown: the extracellular matrix (ECM). ECM provides a suitable space for the survival and activity of cells in the body, and affects the behavior of cells through signal transduction system. Proteoglycans, particularly the small leucine rich proteoglycan (SLRP) family, have been shown to be molecules that play important roles in matrix remodeling and organ fibrosis, such as by affecting ECM components or altering the intracellular environment. But in recent years reports of SLRP families, their manifestations in different organs have not been consistent. Recent studies suggest that proteoglycans entering the blood in a soluble form hold promise as diagnostic biomarkers of organ fibrosis and may provide novel therapeutic strategies for fibrotic diseases. Herein, we discuss and review studies of SLRPs in multi-organ fibrotic diseases.
{"title":"Small Leucine Rich Proteoglycan in Fibrotic Diseases: New Frenemies?","authors":"Jiayu Guo, Yan Wang, Haihai Liang, Baofeng Yang","doi":"10.53941/ijddp.2023.100005","DOIUrl":"https://doi.org/10.53941/ijddp.2023.100005","url":null,"abstract":"Review\u0000Small Leucine Rich Proteoglycan in Fibrotic Diseases: New Frenemies?\u0000\u0000Jiayu Guo 1,2, Yan Wang 1,2, Haihai Liang 1,2,3,*, and Baofeng Yang 1,2,3,*\u0000\u0000\u00001 Department of Pharmacology (National Key Laboratory of Frigid Zone Cardiovascular Diseases), College of Pharmacy, Harbin Medical University, Harbin 150081, China\u00002 Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin 150081, China\u00003 Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2019RU070), Chinese Academy of Medical Sciences, Harbin 150081, China\u0000* Correspondence: lianghaihai@ems.hrbmu.edu.cn (H.H.L),; yangbf@ems.hrbmu.edu.cn (B.F.Y)\u0000 \u0000 \u0000Received: 27 April 2023\u0000Accepted: 2 June 2023\u0000 \u0000\u0000Abstract: The human body is a complex organism with self-regulating ability and can cope with external pressures and challenges. To protect the body from damage during exercise or confrontations, beneath the human epidermal layer, the human body has evolved a coverall gown: the extracellular matrix (ECM). ECM provides a suitable space for the survival and activity of cells in the body, and affects the behavior of cells through signal transduction system. Proteoglycans, particularly the small leucine rich proteoglycan (SLRP) family, have been shown to be molecules that play important roles in matrix remodeling and organ fibrosis, such as by affecting ECM components or altering the intracellular environment. But in recent years reports of SLRP families, their manifestations in different organs have not been consistent. Recent studies suggest that proteoglycans entering the blood in a soluble form hold promise as diagnostic biomarkers of organ fibrosis and may provide novel therapeutic strategies for fibrotic diseases. Herein, we discuss and review studies of SLRPs in multi-organ fibrotic diseases.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"73 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88511823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Review Recent Advances in Natural Plant-based Treatment of Myocardial Ischemia-reperfusion Injury Peixun Yang 1,3,4, Minxuan Liu 2,3,4, Xiaoxue Fan 3,4, Xinzhuang Zhang 3,4, Liang Cao 3,4, Zhenzhong Wang 3,4, and Wei Xiao 3,4, * 1 Kanion School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Avenue Qixia District, Nanjing 210046, China 2 School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue Qixia District, Nanjing 210046, China 3 National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangning Industrial City, Economic and Technological Development Zone of Lianyungang, Lianyungang 222001, China 4 Jiangsu Kanion Pharmaceutical Co Ltd, Jiangning Industrial City, Economic and Technological Development Zone of Lianyungang, Lianyungang 222001, China * Correspondence: xw_kanion@163.com ( Wei Xiao) Received: 23 March 2023 Accepted: 10 May 2023 Abstract: Cardiovascular disease (CDV) is the primary cause of death in the world, and myocardial ischemia (MI) is one of the high-risk CVDs. The myocardial blood supply must be restored as soon as possible to reduce the mortality risk, however, reperfusion itself paradoxically leads to further death of cardiomyocytes and increases the infarct size; this is known as myocardial ischemia/reperfusion injury (MIRI). The pathological mechanism of MIRI is complex, and current research mainly focuses on oxidative stress, dysfunctional mitochondrial energy metabolism, Ca 2+ overload, endoplasmic reticulum stress (ERs) and the inflammatory response. This review briefly summarizes the mechanism of MIRI, and natural plant product (NPP) components proven to ameliorate MIRI and their related signaling pathways. NPPs can alleviate MIRI by regulating oxidative stress, inflammation, ERs, Ca 2+ overload and mitochondrial function maintenance. This review will deepen our understanding of how NPPs reduce MIRI and the future value of NPPs in cardio-protection.
{"title":"Recent Advances in Natural Plant-based Treatment of Myocardial Ischemia-reperfusion Injury","authors":"Peixun Yang, Minxuan Liu, Xiaoxue Fan, Xinzhuang Zhang, Liang Cao, Zhenzhong Wang, W. Xiao","doi":"10.53941/ijddp.2023.100003","DOIUrl":"https://doi.org/10.53941/ijddp.2023.100003","url":null,"abstract":"Review\u0000Recent Advances in Natural Plant-based Treatment of Myocardial Ischemia-reperfusion Injury\u0000\u0000Peixun Yang 1,3,4, Minxuan Liu 2,3,4, Xiaoxue Fan 3,4, Xinzhuang Zhang 3,4, Liang Cao 3,4, Zhenzhong Wang 3,4, and Wei Xiao 3,4, *\u0000\u0000\u00001 Kanion School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Avenue Qixia District, Nanjing 210046, China\u00002 School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue Qixia District, Nanjing 210046, China\u00003 National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangning Industrial City, Economic and Technological Development Zone of Lianyungang, Lianyungang 222001, China\u00004 Jiangsu Kanion Pharmaceutical Co Ltd, Jiangning Industrial City, Economic and Technological Development Zone of Lianyungang, Lianyungang 222001, China\u0000* Correspondence: xw_kanion@163.com ( Wei Xiao)\u0000 \u0000 \u0000Received: 23 March 2023\u0000Accepted: 10 May 2023\u0000 \u0000\u0000Abstract: Cardiovascular disease (CDV) is the primary cause of death in the world, and myocardial ischemia (MI) is one of the high-risk CVDs. The myocardial blood supply must be restored as soon as possible to reduce the mortality risk, however, reperfusion itself paradoxically leads to further death of cardiomyocytes and increases the infarct size; this is known as myocardial ischemia/reperfusion injury (MIRI). The pathological mechanism of MIRI is complex, and current research mainly focuses on oxidative stress, dysfunctional mitochondrial energy metabolism, Ca 2+ overload, endoplasmic reticulum stress (ERs) and the inflammatory response. This review briefly summarizes the mechanism of MIRI, and natural plant product (NPP) components proven to ameliorate MIRI and their related signaling pathways. NPPs can alleviate MIRI by regulating oxidative stress, inflammation, ERs, Ca 2+ overload and mitochondrial function maintenance. This review will deepen our understanding of how NPPs reduce MIRI and the future value of NPPs in cardio-protection.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87771300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Review Pathophysiological Mechanisms and Pharmaceutical Interventions of Myocardial Infarction with Depression Mingyang Xu 1, Yinxiang Wei 2, Zhenhui Wang 1, Yaohui Wang 2, Xiaoming Zhong 3,*, and Qiying Chen 4,* 1 School of medicine, Henan University, Kaifeng 475000, China. 2 Joint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng 475004, China. 3 Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng 475000, China. 4 Department of Cardiology, Huashan Hospital, Fudan University, Shanghai 200040, China. * Correspondence: Xiaoming Zhong (zxm10020202@126.com); Qiying Chen (chenqiying@huashan.org.cn) Received: 23 March 2023 Accepted: 10 May 2023 Abstract: The strong association between acute myocardial infarction (AMI) and major depression disorder（MDD）is a universally accepted. Patients with AMI complicated by MDD often have poor prognosis. Most early studies focused on how AMI leads to MDD, but there are few reports on depression-induced AMI. In terms of mechanism, inflammation, the hypothalamic-pituitary-adrenal axis (HPA axis) and brain-gut axis may be involved in the occurrence and development of MDD after AMI. The inflammatory injury, abnormal sympathetic and vagal nerve activity, HPA axis overactivation, overeating and some therapeutic medicine administration in patients with MDD can also be risk factors for AMI. Both behavioral and pharmaceutical interventions are important for the treatment of AMI with MDD. More drugs are being developed and tested. At present, there are still many issues, needing to be addressed, in the diagnosis, pathogenesis, intervention strategies and therapeutic drugs for AMI with MDD. To aid clinical diagnosis and treatment, this review classifies the existing studies on AMI complicated with MDD, and also includes some of our considerations.
{"title":"Pathophysiological Mechanisms and Pharmaceutical Interventions of Myocardial Infarction with Depression","authors":"Mingyang Xu, Yinxiang Wei, Zhenhui Wang, Yaohui Wang, Xiaoming Zhong, Qiying Chen","doi":"10.53941/ijddp.2023.100004","DOIUrl":"https://doi.org/10.53941/ijddp.2023.100004","url":null,"abstract":"Review\u0000Pathophysiological Mechanisms and Pharmaceutical Interventions of Myocardial Infarction with Depression\u0000\u0000Mingyang Xu 1, Yinxiang Wei 2, Zhenhui Wang 1, Yaohui Wang 2, Xiaoming Zhong 3,*, and Qiying Chen 4,*\u0000\u0000\u00001 School of medicine, Henan University, Kaifeng 475000, China.\u00002 Joint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng 475004, China.\u00003 Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng 475000, China.\u00004 Department of Cardiology, Huashan Hospital, Fudan University, Shanghai 200040, China.\u0000* Correspondence: Xiaoming Zhong (zxm10020202@126.com); Qiying Chen (chenqiying@huashan.org.cn)\u0000 \u0000 \u0000Received: 23 March 2023\u0000Accepted: 10 May 2023\u0000 \u0000\u0000Abstract: The strong association between acute myocardial infarction (AMI) and major depression disorder（MDD）is a universally accepted. Patients with AMI complicated by MDD often have poor prognosis. Most early studies focused on how AMI leads to MDD, but there are few reports on depression-induced AMI. In terms of mechanism, inflammation, the hypothalamic-pituitary-adrenal axis (HPA axis) and brain-gut axis may be involved in the occurrence and development of MDD after AMI. The inflammatory injury, abnormal sympathetic and vagal nerve activity, HPA axis overactivation, overeating and some therapeutic medicine administration in patients with MDD can also be risk factors for AMI. Both behavioral and pharmaceutical interventions are important for the treatment of AMI with MDD. More drugs are being developed and tested. At present, there are still many issues, needing to be addressed, in the diagnosis, pathogenesis, intervention strategies and therapeutic drugs for AMI with MDD. To aid clinical diagnosis and treatment, this review classifies the existing studies on AMI complicated with MDD, and also includes some of our considerations.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"89 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85964398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-27DOI: 10.53941/ijddp.2023.100001
Z. S. Rana, Reena Suman, Shobi Veleri, Pradeep Punnakkal
Review Mechanism of Anti-seizure Medications and Emerging Trends in Epilepsy Treatment Zubin Singh Rana 1, Reena Suman 1, Shobi Veleri 2, and Pradeep Punnakkal 1, * 1 Department of Biophysics, Postgraduate Institute of Medical Education and Research Chandigarh, 160012, India 2 Drug Safety Division, ICMR-National Institute of Nutrition, Hyderabad, 500007, India. * Correspondence: p.pradeep@pgimer.edu.in Received: 28 November 2022 Accepted: 24 January 2023 Abstract: About one percent of the world’s population is affected by epilepsy. Epilepsy-induced psychiatric co-morbidity and mortality impose a huge burden on patients, their families, and society. Anti-seizure medications (ASMs) are drugs used to control seizures in patients with epilepsy. Epilepsy constitutes a spectrum of disorders, with various underlying causes. Hence, finding the right drug to control seizures with minimal side effects is a difficult task for clinicians. Besides controlling seizures, many ASMs have off-target effects that result in unwanted side effects. Compared to first and second-generation drugs, third-generation drugs have shown better tolerance. Even though the target of many ASMs is known, their mechanism of action is not well understood. The main mechanism behind epilepsy is defined as an imbalance in the excitatory-to-inhibitory ratio in neurotransmission. So, the key target of ASMs is the ion channels controlling the intrinsic property of neurons like sodium channels, potassium channels, and calcium channels, the excitatory synaptic transmission via glutamate receptors, and the inhibitory synaptic transmission by GABA receptors. Here we review the role of ion channels in epilepsy, and how the ASMs act on them for seizure control.
{"title":"Mechanism of Anti-seizure Medications and Emerging Trends in Epilepsy Treatment","authors":"Z. S. Rana, Reena Suman, Shobi Veleri, Pradeep Punnakkal","doi":"10.53941/ijddp.2023.100001","DOIUrl":"https://doi.org/10.53941/ijddp.2023.100001","url":null,"abstract":"Review\u0000Mechanism of Anti-seizure Medications and Emerging Trends in Epilepsy Treatment\u0000\u0000Zubin Singh Rana 1, Reena Suman 1, Shobi Veleri 2, and Pradeep Punnakkal 1, *\u0000\u0000\u00001 Department of Biophysics, Postgraduate Institute of Medical Education and Research Chandigarh, 160012, India\u00002 Drug Safety Division, ICMR-National Institute of Nutrition, Hyderabad, 500007, India.\u0000* Correspondence: p.pradeep@pgimer.edu.in\u0000 \u0000 \u0000Received: 28 November 2022\u0000Accepted: 24 January 2023\u0000 \u0000\u0000Abstract: About one percent of the world’s population is affected by epilepsy. Epilepsy-induced psychiatric co-morbidity and mortality impose a huge burden on patients, their families, and society. Anti-seizure medications (ASMs) are drugs used to control seizures in patients with epilepsy. Epilepsy constitutes a spectrum of disorders, with various underlying causes. Hence, finding the right drug to control seizures with minimal side effects is a difficult task for clinicians. Besides controlling seizures, many ASMs have off-target effects that result in unwanted side effects. Compared to first and second-generation drugs, third-generation drugs have shown better tolerance. Even though the target of many ASMs is known, their mechanism of action is not well understood. The main mechanism behind epilepsy is defined as an imbalance in the excitatory-to-inhibitory ratio in neurotransmission. So, the key target of ASMs is the ion channels controlling the intrinsic property of neurons like sodium channels, potassium channels, and calcium channels, the excitatory synaptic transmission via glutamate receptors, and the inhibitory synaptic transmission by GABA receptors. Here we review the role of ion channels in epilepsy, and how the ASMs act on them for seizure control.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73923511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01Epub Date: 2023-01-11DOI: 10.53941/ijddp.0201003
Antoinette Holland, Molly Enrick, Arianna Diaz, Liya Yin
microRNA-21 (miR-21) serves a multitude of functions at the molecular level through its regulation of messenger RNA. Previous research has sparked interest in the role of miR-21 as a potential therapeutic target in cardiovascular diseases. miR-21 expression contributes to the differentiation, proliferation, and maturation of many cell types, such as fibroblasts, endothelial cells, cardiomyocytes, and endothelial progenitor cells. The function of miR-21 depends upon its expression level in the specific cell types and downstream targets, which determine cell fate. Under pathological conditions, the expression level of miR-21 is altered, leading to abnormal gene regulation of downstream signaling and cardiovascular diseases such as hypertension, cardiac hypertrophy and fibrosis, atherosclerosis, and heart failure. Agomirs or antagomirs can be introduced into the respective tissue type to reverse or stop the progression of the disease. Exosomes in the extracellular vesicles, which mediate many cellular events with high biocompatibility, have a high potential of efficiently delivering miR-21 to their targeted cells. The critical role of miR-21 in cardiovascular disease (CVD) is indisputable, but there are controversial reports on the function of miR-21 in the same disease. This discrepancy sparks interest in better understanding the role of miR-21 in different tissues under different stages of various diseases and the mechanism of how miR-21 inhibitors work.
{"title":"Is miR-21 A Therapeutic Target in Cardiovascular Disease?","authors":"Antoinette Holland, Molly Enrick, Arianna Diaz, Liya Yin","doi":"10.53941/ijddp.0201003","DOIUrl":"10.53941/ijddp.0201003","url":null,"abstract":"<p><p>microRNA-21 (miR-21) serves a multitude of functions at the molecular level through its regulation of messenger RNA. Previous research has sparked interest in the role of miR-21 as a potential therapeutic target in cardiovascular diseases. miR-21 expression contributes to the differentiation, proliferation, and maturation of many cell types, such as fibroblasts, endothelial cells, cardiomyocytes, and endothelial progenitor cells. The function of miR-21 depends upon its expression level in the specific cell types and downstream targets, which determine cell fate. Under pathological conditions, the expression level of miR-21 is altered, leading to abnormal gene regulation of downstream signaling and cardiovascular diseases such as hypertension, cardiac hypertrophy and fibrosis, atherosclerosis, and heart failure. Agomirs or antagomirs can be introduced into the respective tissue type to reverse or stop the progression of the disease. Exosomes in the extracellular vesicles, which mediate many cellular events with high biocompatibility, have a high potential of efficiently delivering miR-21 to their targeted cells. The critical role of miR-21 in cardiovascular disease (CVD) is indisputable, but there are controversial reports on the function of miR-21 in the same disease. This discrepancy sparks interest in better understanding the role of miR-21 in different tissues under different stages of various diseases and the mechanism of how miR-21 inhibitors work.</p>","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"2 1","pages":"26-36"},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41169497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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