Pub Date : 2024-07-01DOI: 10.1097/FJC.0000000000001585
Mattia Galli, Sebastiano Sciarretta, Giacomo Frati, Giuseppe Biondi-Zoccai
{"title":"Reevaluating Anticoagulation in Antiphospholipid Syndrome: The Role of Apixaban in the Current Treatment Paradigm.","authors":"Mattia Galli, Sebastiano Sciarretta, Giacomo Frati, Giuseppe Biondi-Zoccai","doi":"10.1097/FJC.0000000000001585","DOIUrl":"10.1097/FJC.0000000000001585","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1097/FJC.0000000000001568
Chenxin Zeng, Jiangfeng Wu, Junming Li
Abstract: Adult animals are unable to regenerate heart cells due to postnatal cardiomyocyte cycle arrest, leading to higher mortality rates in cardiomyopathy. However, reprogramming of energy metabolism in cardiomyocytes provides a new perspective on the contribution of glycolysis to repair, regeneration, and fibrosis after cardiac injury. Pyruvate kinase (PK) is a key enzyme in the glycolysis process. This review focuses on the glycolysis function of PKM2, although PKM1 and PKM2 both play significant roles in the process after cardiac injury. PKM2 exists in both low-activity dimer and high-activity tetramer forms. PKM2 dimers promote aerobic glycolysis but have low catalytic activity, leading to the accumulation of glycolytic intermediates. These intermediates enter the pentose phosphate pathway to promote cardiomyocyte proliferation and heart regeneration. Additionally, they activate adenosine triphosphate (ATP)-sensitive K + (K ATP ) channels, protecting the heart against ischemic damage. PKM2 tetramers function similar to PKM1 in glycolysis, promoting pyruvate oxidation and subsequently ATP generation to protect the heart from ischemic damage. They also activate KDM5 through the accumulation of αKG, thereby promoting cardiomyocyte proliferation and cardiac regeneration. Apart from glycolysis, PKM2 interacts with transcription factors like Jmjd4, RAC1, β-catenin, and hypoxia-inducible factor (HIF)-1α, playing various roles in homeostasis maintenance, remodeling, survival regulation, and neovascularization promotion. However, PKM2 has also been implicated in promoting cardiac fibrosis through mechanisms like sirtuin (SIRT) 3 deletion, TG2 expression enhancement, and activation of transforming growth factor-β1 (TGF-β1)/Smad2/3 and Jak2/Stat3 signals. Overall, PKM2 shows promising potential as a therapeutic target for promoting cardiomyocyte proliferation and cardiac regeneration and addressing cardiac fibrosis after injury.
{"title":"Pyruvate Kinase M2: A Potential Regulator of Cardiac Injury Through Glycolytic and Non-glycolytic Pathways.","authors":"Chenxin Zeng, Jiangfeng Wu, Junming Li","doi":"10.1097/FJC.0000000000001568","DOIUrl":"10.1097/FJC.0000000000001568","url":null,"abstract":"<p><strong>Abstract: </strong>Adult animals are unable to regenerate heart cells due to postnatal cardiomyocyte cycle arrest, leading to higher mortality rates in cardiomyopathy. However, reprogramming of energy metabolism in cardiomyocytes provides a new perspective on the contribution of glycolysis to repair, regeneration, and fibrosis after cardiac injury. Pyruvate kinase (PK) is a key enzyme in the glycolysis process. This review focuses on the glycolysis function of PKM2, although PKM1 and PKM2 both play significant roles in the process after cardiac injury. PKM2 exists in both low-activity dimer and high-activity tetramer forms. PKM2 dimers promote aerobic glycolysis but have low catalytic activity, leading to the accumulation of glycolytic intermediates. These intermediates enter the pentose phosphate pathway to promote cardiomyocyte proliferation and heart regeneration. Additionally, they activate adenosine triphosphate (ATP)-sensitive K + (K ATP ) channels, protecting the heart against ischemic damage. PKM2 tetramers function similar to PKM1 in glycolysis, promoting pyruvate oxidation and subsequently ATP generation to protect the heart from ischemic damage. They also activate KDM5 through the accumulation of αKG, thereby promoting cardiomyocyte proliferation and cardiac regeneration. Apart from glycolysis, PKM2 interacts with transcription factors like Jmjd4, RAC1, β-catenin, and hypoxia-inducible factor (HIF)-1α, playing various roles in homeostasis maintenance, remodeling, survival regulation, and neovascularization promotion. However, PKM2 has also been implicated in promoting cardiac fibrosis through mechanisms like sirtuin (SIRT) 3 deletion, TG2 expression enhancement, and activation of transforming growth factor-β1 (TGF-β1)/Smad2/3 and Jak2/Stat3 signals. Overall, PKM2 shows promising potential as a therapeutic target for promoting cardiomyocyte proliferation and cardiac regeneration and addressing cardiac fibrosis after injury.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1097/FJC.0000000000001562
Lu Gao, Qi Wang, Min-Yi Li, Meng-Meng Zhang, Bin Wang, Tai-Wei Dong, Pei-Feng Wei, Min Li
Abstract: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. CVD and kidney disease are closely related, with kidney injury increasing CVD mortality. The pathogenesis of cardiovascular and renal diseases involves complex and diverse interactions between multiple extracellular and intracellular signaling molecules, among which transient receptor potential vanilloid 1 (TRPV1)/transient receptor potential ankyrin 1 (TRPA1) channels have received increasing attention. TRPV1 belongs to the vanilloid receptor subtype family of transient receptor potential ion channels, and TRPA1 belongs to the transient receptor potential channel superfamily. TRPV1/TRPA1 are jointly involved in the management of cardiovascular and renal diseases and play important roles in regulating vascular tension, promoting angiogenesis, antifibrosis, anti-inflammation, and antioxidation. The mechanism of TRPV1/TRPA1 is mainly related to regulation of intracellular calcium influx and release of nitric oxide and calcitonin gene-related peptide. Therefore, this study takes the TRPV1/TRPA1 channel as the research object, analyzes and summarizes the process and mechanism of TRPV1/TRPA1 affecting cardiovascular and renal diseases, and lays a foundation for the treatment of cardiorenal diseases.
{"title":"A Mechanism for the Treatment of Cardiovascular and Renal Disease: TRPV1 and TRPA1.","authors":"Lu Gao, Qi Wang, Min-Yi Li, Meng-Meng Zhang, Bin Wang, Tai-Wei Dong, Pei-Feng Wei, Min Li","doi":"10.1097/FJC.0000000000001562","DOIUrl":"10.1097/FJC.0000000000001562","url":null,"abstract":"<p><strong>Abstract: </strong>Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. CVD and kidney disease are closely related, with kidney injury increasing CVD mortality. The pathogenesis of cardiovascular and renal diseases involves complex and diverse interactions between multiple extracellular and intracellular signaling molecules, among which transient receptor potential vanilloid 1 (TRPV1)/transient receptor potential ankyrin 1 (TRPA1) channels have received increasing attention. TRPV1 belongs to the vanilloid receptor subtype family of transient receptor potential ion channels, and TRPA1 belongs to the transient receptor potential channel superfamily. TRPV1/TRPA1 are jointly involved in the management of cardiovascular and renal diseases and play important roles in regulating vascular tension, promoting angiogenesis, antifibrosis, anti-inflammation, and antioxidation. The mechanism of TRPV1/TRPA1 is mainly related to regulation of intracellular calcium influx and release of nitric oxide and calcitonin gene-related peptide. Therefore, this study takes the TRPV1/TRPA1 channel as the research object, analyzes and summarizes the process and mechanism of TRPV1/TRPA1 affecting cardiovascular and renal diseases, and lays a foundation for the treatment of cardiorenal diseases.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1097/FJC.0000000000001519
Siyi Li, Qingjie Xin, Yan Yan, Xiao Wang, Hui Ai, Bin Que, Wei Gong, Shaoping Nie
Abstract: The role of phosphodiesterase 5 (Pde5) in obstructive sleep apnea-induced damage remains unclear. Our study aimed to investigate the role of Pde5 in the chronic intermittent hypoxia (CIH) model. C57BL/6J wild-type (WT) mice (n = 48) and Pde5 knockout (Pde5 -/- ) mice (n = 24) were randomly assigned to CIH group and room air group. After 6 weeks, some WT mice (n = 24) in CIH group were given sildenafil or saline gavage for another 4 weeks. Blood pressure was regularly measured during the experiment. Echocardiography was used to estimate cardiac function. We collected organs from each group of mice and measured their physical indicators. Histochemical staining was used to explore the size of cardiomyocyte and fibrosis area of various organs. Cyclic guanosine monophosphate and malondialdehyde concentrations in serum were measured by ELISA assay. Compared with the RA-treated group, the 6-week CIH resulted in a significant increase in blood pressure, altered heart structure, and reduced serum cyclic guanosine monophosphate in WT mice. Pde5 -/- mice and sildenafil intragastric administration significantly reduced systolic blood pressure in CIH condition and attenuated the damage of target organs. In CIH model, we found that the cardiomyocyte size and fibrosis area of heart and kidney significantly reduced in Pde5 -/- groups. Besides, endogenous and exogenous inhibition of Pde5 reduced malondialdehyde level and inflammatory and oxidative stress markers expression in CIH condition. In this study, we found that Pde5 inhibition could reduce blood pressure and alleviate target organ damage in the CIH model, which may be mediated through the oxidative stress pathway.
{"title":"Pde5 Inhibition Reduced Blood Pressure and Alleviated Target Organ Damage in Chronic Intermittent Hypoxia.","authors":"Siyi Li, Qingjie Xin, Yan Yan, Xiao Wang, Hui Ai, Bin Que, Wei Gong, Shaoping Nie","doi":"10.1097/FJC.0000000000001519","DOIUrl":"10.1097/FJC.0000000000001519","url":null,"abstract":"<p><strong>Abstract: </strong>The role of phosphodiesterase 5 (Pde5) in obstructive sleep apnea-induced damage remains unclear. Our study aimed to investigate the role of Pde5 in the chronic intermittent hypoxia (CIH) model. C57BL/6J wild-type (WT) mice (n = 48) and Pde5 knockout (Pde5 -/- ) mice (n = 24) were randomly assigned to CIH group and room air group. After 6 weeks, some WT mice (n = 24) in CIH group were given sildenafil or saline gavage for another 4 weeks. Blood pressure was regularly measured during the experiment. Echocardiography was used to estimate cardiac function. We collected organs from each group of mice and measured their physical indicators. Histochemical staining was used to explore the size of cardiomyocyte and fibrosis area of various organs. Cyclic guanosine monophosphate and malondialdehyde concentrations in serum were measured by ELISA assay. Compared with the RA-treated group, the 6-week CIH resulted in a significant increase in blood pressure, altered heart structure, and reduced serum cyclic guanosine monophosphate in WT mice. Pde5 -/- mice and sildenafil intragastric administration significantly reduced systolic blood pressure in CIH condition and attenuated the damage of target organs. In CIH model, we found that the cardiomyocyte size and fibrosis area of heart and kidney significantly reduced in Pde5 -/- groups. Besides, endogenous and exogenous inhibition of Pde5 reduced malondialdehyde level and inflammatory and oxidative stress markers expression in CIH condition. In this study, we found that Pde5 inhibition could reduce blood pressure and alleviate target organ damage in the CIH model, which may be mediated through the oxidative stress pathway.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1097/FJC.0000000000001600
Kaneez Fatima, Aayat Ellahi, Mariam Adil, Haider Kashif, Muhammad Uzair, Naela Ashraf, Mehak Barolia, Mujtaba Hyder, Areeba Nakhuda, Michelle Ayub, Sofia Jamil Butt, Ahmed Mustafa Rashid
Renin-angiotensin-system inhibitors (RASi), specifically angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs), are widely used anti-hypertensives. Their impact on the prognostic outcomes among cancer patients has been subject to scrutiny and debate. The aim of this study is to evaluate the effect of RASi on survival in cancer patients. We systematically searched PubMed, Web of Science, Embase and Cochrane Library for relevant studies published until April 1st, 2022. All the studies, interventional or observational, which examined effects of ARBs and ACEi on cancer prognosis compared to a control group and reported the survival outcomes and Hazards Ratios were included in the analysis. From each study, pooled hazard ratios (HR) with corresponding 95% confidence intervals (95% CI) were identified and collected. Subgroup analysis was conducted to investigate heterogeneity. Sixty-one studies were included in this meta-analysis. Data of 343,283 participants were used in the study. It was found that RASi improved overall survival (OS) (HR=0.88; 95% CI: 0.82-0.93; P<0.0001), progression free survival (PFS) (HR=0.72; 95% CI: 0.65-0.79; P<0.00001), disease specific survival (DSS) (HR=0.86; 95% CI: 0.71-1.04; P=0.03), and recurrence free survival (RFS) (HR=0.74; 95% CI: 0.58-0.93; P=0.01) in cancer patients. The effect of RASi on OS varied depending on the type of cancer or type of RASi (ACEi or ARBs), according to subgroup analysis. The usage of RAS inhibitors has a positive impact on survival outcomes and recurrence among cancer patients.
{"title":"The potential impact of renin-angiotensin system inhibitors on cancer survival and recurrence: A systemic review and meta-analysis.","authors":"Kaneez Fatima, Aayat Ellahi, Mariam Adil, Haider Kashif, Muhammad Uzair, Naela Ashraf, Mehak Barolia, Mujtaba Hyder, Areeba Nakhuda, Michelle Ayub, Sofia Jamil Butt, Ahmed Mustafa Rashid","doi":"10.1097/FJC.0000000000001600","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001600","url":null,"abstract":"<p><p>Renin-angiotensin-system inhibitors (RASi), specifically angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs), are widely used anti-hypertensives. Their impact on the prognostic outcomes among cancer patients has been subject to scrutiny and debate. The aim of this study is to evaluate the effect of RASi on survival in cancer patients. We systematically searched PubMed, Web of Science, Embase and Cochrane Library for relevant studies published until April 1st, 2022. All the studies, interventional or observational, which examined effects of ARBs and ACEi on cancer prognosis compared to a control group and reported the survival outcomes and Hazards Ratios were included in the analysis. From each study, pooled hazard ratios (HR) with corresponding 95% confidence intervals (95% CI) were identified and collected. Subgroup analysis was conducted to investigate heterogeneity. Sixty-one studies were included in this meta-analysis. Data of 343,283 participants were used in the study. It was found that RASi improved overall survival (OS) (HR=0.88; 95% CI: 0.82-0.93; P<0.0001), progression free survival (PFS) (HR=0.72; 95% CI: 0.65-0.79; P<0.00001), disease specific survival (DSS) (HR=0.86; 95% CI: 0.71-1.04; P=0.03), and recurrence free survival (RFS) (HR=0.74; 95% CI: 0.58-0.93; P=0.01) in cancer patients. The effect of RASi on OS varied depending on the type of cancer or type of RASi (ACEi or ARBs), according to subgroup analysis. The usage of RAS inhibitors has a positive impact on survival outcomes and recurrence among cancer patients.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Panax notoginseng has the effect of stimulating circulation to end stasis. Our study was designed to evaluate the anti-thrombotic effect of protoparaxotriol saponins (PTS) from Panax notoginseng and the involved mechanisms. A thrombosis model was constructed, and the anti-thrombotic activity of PTS was determined by erythrocyte staining, heart rate, and blood flow velocity. In addition, quantitative real-time polymerase chain reaction (qPCR) was used to identify changes in the expression of genes related to coagulation, inflammation, and apoptosis. PTS alleviated arachidonic acid (AA)-induced caudal vein thrombosis, restored blood flow, and increased the area of cardiac erythrocyte staining, heart rate and blood flow velocity. It reduced the ponatinib-induced cerebral thrombus area and decreased the intensity of erythrocyte staining. The qPCR data showed that the anti-thrombotic effect of PTS was mediated by suppression of genes related to coagulation, inflammation and apoptosis, and also involved inhibition of NF-κB and PI3K/Akt pathways.
{"title":"Anti-thrombotic effect of protoparaxotriol saponins from Panax notoginseng using zebrafish model.","authors":"Xin Liu, Wei Fan, Shenghua Lin, Jiayu Chen, Shanshan Zhang, Xiaobin Li, Meng Jin, Qiuxia He","doi":"10.1097/FJC.0000000000001604","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001604","url":null,"abstract":"<p><p>Panax notoginseng has the effect of stimulating circulation to end stasis. Our study was designed to evaluate the anti-thrombotic effect of protoparaxotriol saponins (PTS) from Panax notoginseng and the involved mechanisms. A thrombosis model was constructed, and the anti-thrombotic activity of PTS was determined by erythrocyte staining, heart rate, and blood flow velocity. In addition, quantitative real-time polymerase chain reaction (qPCR) was used to identify changes in the expression of genes related to coagulation, inflammation, and apoptosis. PTS alleviated arachidonic acid (AA)-induced caudal vein thrombosis, restored blood flow, and increased the area of cardiac erythrocyte staining, heart rate and blood flow velocity. It reduced the ponatinib-induced cerebral thrombus area and decreased the intensity of erythrocyte staining. The qPCR data showed that the anti-thrombotic effect of PTS was mediated by suppression of genes related to coagulation, inflammation and apoptosis, and also involved inhibition of NF-κB and PI3K/Akt pathways.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-04DOI: 10.1097/fjc.0000000000001598
Xiu-li Zhang, Jia-peng Li, Mei-zhu Wu, Jin-kong Wu, Shu-yu He, Yao Lu, Qi-hang Ding, Yingling Wen, Lin-zi Long, Chang-geng Fu, A. Farman, A-ling Shen, Jun Peng
Quercetin is kown for its antihypertensive effects. However, its role on hypertensive renal injury has not been fully eucidated. In this study, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and Annexin V staining were used to assess the pathological changes and cells apoptosis in the renal tissues of Ang II-infused mice and Ang II- stimulated renal tubular epithelial cell line (NRK-52E). A variety of technologies, including network pharmacology, RNA-sequencing, immunohistochemistry, and Western blotting were performed to investigate its underlying mechanisms. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2 and Bax) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Quercetin treatment significantly alleviated the pathological changes in renal tissues of Ang II-infused mice and reversed 464 differentially expressed transcripts (DETs), as well as enriched several signaling pathways, including those related apoptosis and p53 pathway. Furthermore, quercetin treatment significantly inhibited the cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Additionally, quercetin treatment inhibited the upregulation of p53, Bax, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Moreover, the molecular docking results indicated a potential binding interaction between quercetin and TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells, and by targeting p53 may be one of the potential underlying mechanisms.
槲皮素因其抗高血压作用而闻名。然而,槲皮素对高血压肾损伤的作用尚未完全阐明。本研究采用苏木精和伊红染色、末端脱氧核苷酸转移酶(TdT)dUTP缺口末端标记(TUNEL)染色和Annexin V染色来评估血管紧张素II注射小鼠肾组织和血管紧张素II刺激的肾小管上皮细胞系(NRK-52E)的病理变化和细胞凋亡。研究人员采用了多种技术,包括网络药理学、RNA 序列分析、免疫组织化学和 Western 印迹分析,以探究其潜在机制。网络药理学分析发现了多个潜在候选靶点(包括TP53、Bcl-2和Bax)和丰富的信号通路(包括细胞凋亡和p53信号通路)。槲皮素治疗明显缓解了血管紧张素II注射小鼠肾组织的病理变化,逆转了464个差异表达转录本(DETs),并丰富了多个信号通路,包括与细胞凋亡和p53通路相关的信号通路。此外,槲皮素还能明显抑制血管紧张素II注射小鼠肾组织和血管紧张素II刺激的NRK-52E细胞的细胞凋亡。此外,槲皮素还能抑制血管紧张素II注射小鼠肾组织和血管紧张素II刺激的NRK-52E细胞中p53、Bax、裂解天冬酶-9和裂解天冬酶-3蛋白表达的上调和Bcl-2蛋白表达的下调。此外,分子对接结果表明,槲皮素与 TP53 之间存在潜在的结合相互作用。槲皮素能明显减轻血管紧张素II灌注小鼠肾组织和血管紧张素II刺激的NRK-52E细胞的高血压肾损伤和细胞凋亡,靶向p53可能是其潜在的内在机制之一。
{"title":"Quercetin protects against hypertensive renal injury by attenuating apoptosis: an integrated approach using network pharmacology and RNA-Seq","authors":"Xiu-li Zhang, Jia-peng Li, Mei-zhu Wu, Jin-kong Wu, Shu-yu He, Yao Lu, Qi-hang Ding, Yingling Wen, Lin-zi Long, Chang-geng Fu, A. Farman, A-ling Shen, Jun Peng","doi":"10.1097/fjc.0000000000001598","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001598","url":null,"abstract":"Quercetin is kown for its antihypertensive effects. However, its role on hypertensive renal injury has not been fully eucidated. In this study, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and Annexin V staining were used to assess the pathological changes and cells apoptosis in the renal tissues of Ang II-infused mice and Ang II- stimulated renal tubular epithelial cell line (NRK-52E). A variety of technologies, including network pharmacology, RNA-sequencing, immunohistochemistry, and Western blotting were performed to investigate its underlying mechanisms. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2 and Bax) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Quercetin treatment significantly alleviated the pathological changes in renal tissues of Ang II-infused mice and reversed 464 differentially expressed transcripts (DETs), as well as enriched several signaling pathways, including those related apoptosis and p53 pathway. Furthermore, quercetin treatment significantly inhibited the cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Additionally, quercetin treatment inhibited the upregulation of p53, Bax, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Moreover, the molecular docking results indicated a potential binding interaction between quercetin and TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells, and by targeting p53 may be one of the potential underlying mechanisms.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141387259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1097/FJC.0000000000001565
Ubong S Ekperikpe, Sautan Mandal, Anukool A Bhopatkar, Corbin A Shields, Chantell A Coley, Christy L Chambers, Tyler D Johnson, Denise C Cornelius, Jan M Williams
Abstract: Prepubertal obesity is growing at an alarming rate and is now considered a risk factor for renal injury. Recently, we reported that the early development of renal injury in obese Dahl salt-sensitive (SS) leptin receptor mutant (SS LepR mutant) rats was associated with increased T-cell infiltration and activation before puberty. Therefore, the current study investigated the effect of inhibiting T-cell activation with abatacept on the progression of renal injury in young obese SS LepR mutant rats before puberty. Four-week-old SS and SS LepR mutant rats were treated with IgG or abatacept (1 mg/kg; ip, every other day) for 4 weeks. Abatacept reduced the renal infiltration of T cells by almost 50% in SS LepR mutant rats. Treatment with abatacept decreased the renal expression of macrophage inflammatory protein-3 alpha while increasing IL-4 in SS LepR mutant rats without affecting SS rats. While not having an impact on blood glucose levels, abatacept reduced hyperinsulinemia and plasma triglycerides in SS LepR mutant rats without affecting SS rats. We did not observe any differences in the mean arterial pressure among the groups. Proteinuria was markedly higher in SS LepR mutant rats than in SS rats throughout the study, and treatment with abatacept decreased proteinuria by about 40% in SS LepR mutant rats without affecting SS rats. We observed significant increases in glomerular and tubular injury and renal fibrosis in SS LepR mutant rats versus SS rats, and chronic treatment with abatacept significantly reduced these renal abnormalities in SS LepR mutant rats. These data suggest that renal T-cell activation contributes to the early progression of renal injury associated with prepubertal obesity.
摘要:青春期前肥胖(PPO)正以惊人的速度增长,目前已被认为是肾损伤的一个危险因素。最近,我们报道了肥胖的达尔盐敏感瘦素受体突变体(SSLepRmutant)大鼠肾损伤的早期发展与青春期前T细胞浸润和激活增加有关。因此,本研究探讨了用阿巴他赛普抑制T细胞活化对青春期前肥胖SSLepRmutant大鼠肾损伤进展的影响。用 IgG 或阿巴他赛(1 毫克/千克;ip,隔日一次)治疗四周大的 SS 和 SSLepRmutant 大鼠。阿巴他赛能使 SSLepRmutant 大鼠肾脏的 T 细胞浸润减少近 50%。阿巴他赛普能降低巨噬细胞炎症蛋白-3α(MIP-3α)在SSLepRmutant大鼠肾脏的表达,同时增加IL-4,但对SS大鼠没有影响。虽然阿巴他赛普对血糖没有影响,但它降低了 SSLepRmutant 大鼠的高胰岛素血症和血浆甘油三酯,而对 SS 大鼠没有影响。我们没有观察到各组之间的 MAP 有任何差异。在整个研究过程中,SSLepRmutant 大鼠的蛋白尿明显高于 SS 大鼠,阿巴他赛普治疗可使 SSLepRmutant 大鼠的蛋白尿减少约 40%,但对 SS 大鼠没有影响。我们观察到 SSLepRmutant 大鼠与 SS 大鼠相比,肾小球和肾小管损伤及肾纤维化明显增加,而阿巴他赛普的长期治疗可显著减少 SSLepRmutant 大鼠的这些肾脏异常。这些数据表明,肾T细胞活化导致了与PPO相关的肾损伤的早期进展。
{"title":"Abatacept Decreases Renal T-cell Infiltration and Renal Inflammation and Ameliorates Progressive Renal Injury in Obese Dahl Salt-sensitive Rats Before Puberty.","authors":"Ubong S Ekperikpe, Sautan Mandal, Anukool A Bhopatkar, Corbin A Shields, Chantell A Coley, Christy L Chambers, Tyler D Johnson, Denise C Cornelius, Jan M Williams","doi":"10.1097/FJC.0000000000001565","DOIUrl":"10.1097/FJC.0000000000001565","url":null,"abstract":"<p><strong>Abstract: </strong>Prepubertal obesity is growing at an alarming rate and is now considered a risk factor for renal injury. Recently, we reported that the early development of renal injury in obese Dahl salt-sensitive (SS) leptin receptor mutant (SS LepR mutant) rats was associated with increased T-cell infiltration and activation before puberty. Therefore, the current study investigated the effect of inhibiting T-cell activation with abatacept on the progression of renal injury in young obese SS LepR mutant rats before puberty. Four-week-old SS and SS LepR mutant rats were treated with IgG or abatacept (1 mg/kg; ip, every other day) for 4 weeks. Abatacept reduced the renal infiltration of T cells by almost 50% in SS LepR mutant rats. Treatment with abatacept decreased the renal expression of macrophage inflammatory protein-3 alpha while increasing IL-4 in SS LepR mutant rats without affecting SS rats. While not having an impact on blood glucose levels, abatacept reduced hyperinsulinemia and plasma triglycerides in SS LepR mutant rats without affecting SS rats. We did not observe any differences in the mean arterial pressure among the groups. Proteinuria was markedly higher in SS LepR mutant rats than in SS rats throughout the study, and treatment with abatacept decreased proteinuria by about 40% in SS LepR mutant rats without affecting SS rats. We observed significant increases in glomerular and tubular injury and renal fibrosis in SS LepR mutant rats versus SS rats, and chronic treatment with abatacept significantly reduced these renal abnormalities in SS LepR mutant rats. These data suggest that renal T-cell activation contributes to the early progression of renal injury associated with prepubertal obesity.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1097/FJC.0000000000001520
Wei Zhang, Wei Zhang, Ning Gu, Zhimei Qiu, Li Pan, Yongchao Zhao, Bei Shi
Abstract: The mechanism of in-stent restenosis (ISR) remains elusive, and in-stent neoatherosclerosis (ISNA) may hold significant pathophysiologic implications. Nevertheless, the correlation between ISNA and the progression of untreated coronary segments affected by native atherosclerosis remains incompletely investigated. This study enrolled 225 patients diagnosed with coronary heart disease and multivessel disease. These patients underwent successful percutaneous coronary intervention and intraoperative placement of the drug-eluting stent, followed by optical coherence tomography assessment of the culprit stent. The mechanism of ISR was examined through qualitative and quantitative analysis of optical coherence tomography imaging. A significantly higher proportion of patients in the ISR with nontarget lesion progression (N-TLP) group exhibited lipid plaque formation compared with the ISR without N-TLP group (69.0% vs. 39.8%, P < 0.001). The incidence of thin-cap fibroatheroma (33.3% vs. 11.4%, P = 0.001) and ISNA (60.7% vs. 38.6%, P < 0.001) was markedly elevated in the ISR with N-TLP group compared with the ISR without N-TLP group. Regarding manifestations, heterogeneous hyperplasia was predominantly observed in the ISR with N-TLP group (76.2% vs. 38.6%, P < 0.001), whereas homogeneous hyperplasia was primarily presented in the ISR without N-TLP group (61.4% vs. 23.8%, P < 0.001). Patients displaying notable progression of naturally occurring atherosclerosis manifest histomorphologic features of ISR, primarily characterized by heterogeneous intimal hyperplasia and a higher prevalence of ISNA. In contrast, patients without substantial progression of naturally occurring atherosclerosis exhibit histomorphologic features of ISR primarily characterized by homogeneous intimal hyperplasia.
{"title":"Naturally Occurring Atherosclerosis Progression and In-stent Restenosis: Exploring Histomorphologic Associations Using Optical Coherence Tomography.","authors":"Wei Zhang, Wei Zhang, Ning Gu, Zhimei Qiu, Li Pan, Yongchao Zhao, Bei Shi","doi":"10.1097/FJC.0000000000001520","DOIUrl":"10.1097/FJC.0000000000001520","url":null,"abstract":"<p><strong>Abstract: </strong>The mechanism of in-stent restenosis (ISR) remains elusive, and in-stent neoatherosclerosis (ISNA) may hold significant pathophysiologic implications. Nevertheless, the correlation between ISNA and the progression of untreated coronary segments affected by native atherosclerosis remains incompletely investigated. This study enrolled 225 patients diagnosed with coronary heart disease and multivessel disease. These patients underwent successful percutaneous coronary intervention and intraoperative placement of the drug-eluting stent, followed by optical coherence tomography assessment of the culprit stent. The mechanism of ISR was examined through qualitative and quantitative analysis of optical coherence tomography imaging. A significantly higher proportion of patients in the ISR with nontarget lesion progression (N-TLP) group exhibited lipid plaque formation compared with the ISR without N-TLP group (69.0% vs. 39.8%, P < 0.001). The incidence of thin-cap fibroatheroma (33.3% vs. 11.4%, P = 0.001) and ISNA (60.7% vs. 38.6%, P < 0.001) was markedly elevated in the ISR with N-TLP group compared with the ISR without N-TLP group. Regarding manifestations, heterogeneous hyperplasia was predominantly observed in the ISR with N-TLP group (76.2% vs. 38.6%, P < 0.001), whereas homogeneous hyperplasia was primarily presented in the ISR without N-TLP group (61.4% vs. 23.8%, P < 0.001). Patients displaying notable progression of naturally occurring atherosclerosis manifest histomorphologic features of ISR, primarily characterized by heterogeneous intimal hyperplasia and a higher prevalence of ISNA. In contrast, patients without substantial progression of naturally occurring atherosclerosis exhibit histomorphologic features of ISR primarily characterized by homogeneous intimal hyperplasia.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1097/FJC.0000000000001494
Yumeko Kawano, Maria A Pabón, Candace H Feldman, Sarah Cuddy, Leonard S Lilly, Michael S Garshick, Brittany Weber
Abstract: This review summarizes the evaluation for underlying rheumatic conditions in patients presenting with acute pericarditis, treatment considerations for specific rheumatic conditions, and the role of imaging in diagnosis and monitoring. Pericarditis may be one of the initial presentations of a rheumatic disease or identified in a patient with known rheumatic disease. There is also growing evidence for using anti-inflammatory and immunosuppressive agents for treating recurrent pericarditis, which can overlap with the treatment of rheumatic diseases.
{"title":"Evaluation and Management of Pericarditis in Rheumatic Diseases.","authors":"Yumeko Kawano, Maria A Pabón, Candace H Feldman, Sarah Cuddy, Leonard S Lilly, Michael S Garshick, Brittany Weber","doi":"10.1097/FJC.0000000000001494","DOIUrl":"10.1097/FJC.0000000000001494","url":null,"abstract":"<p><strong>Abstract: </strong>This review summarizes the evaluation for underlying rheumatic conditions in patients presenting with acute pericarditis, treatment considerations for specific rheumatic conditions, and the role of imaging in diagnosis and monitoring. Pericarditis may be one of the initial presentations of a rheumatic disease or identified in a patient with known rheumatic disease. There is also growing evidence for using anti-inflammatory and immunosuppressive agents for treating recurrent pericarditis, which can overlap with the treatment of rheumatic diseases.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11001789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}