Pub Date : 2024-05-23DOI: 10.53941/ijddp.2024.100006
Angela Clerk
Review Inhibiting the Extracellular Signal-regulated Kinase 1/2 (ERK1/2) Cascade in Cancer and the Heart: for Better or Worse, in Sickness and Health? Angela Clerk *, Shona U Amadi, Samuel J Smith, and Peter H Sugden School of Biological Sciences, University of Reading, Reading RG6 6AS, UK * Correspondence: a.clerk@reading.ac.uk Received: 3 April 2024; Revised: 27 April 2024; Accepted: 29 April 2024; Published: 23 May 2024 Abstract: The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are the prototypic mitogen-activated protein kinases, first discovered and investigated in the context of cell division and their role in cancer. ERK1/2 are phosphorylated and activated by upstream kinases, MEK1/2 (also known as MKK1/2) that are in turn phosphorylated and activated by RAF kinases (RAF1, BRAF, ARAF), these being activated by small G proteins of the RAS family (HRAS, KRAS, NRAS). The oncogenic nature of the pathway has resulted in the generation of highly specific inhibitors that are successfully used to treat cancer, particularly melanoma. Those in clinical use currently inhibit some isoforms of RAS, RAF kinases and MEK1/2, with additional inhibitors of these kinases in clinical trials. New drugs are now entering the clinic to inhibit ERK1/2 themselves. The ERK1/2 cascade is also important in the heart. It promotes cardiomyocyte hypertrophy and cardioprotection to counter pathophysiological stresses, and plays a significant role in enhancing cardiac fibrosis with detrimental consequences for cardiac function. Here, we summarise the role of ERK1/2 signalling in cancer and the heart, we outline the development of ERK1/2 cascade inhibitors for cancer providing information on those that are approved as cancer treatments and those which are in clinical trials, and we discuss the known and predicted consequences of these ERK1/2 cascade inhibitors for the heart. Integral with this, we consider whether these drugs are necessarily detrimental to the heart or if/when they may be repurposed to prevent or treat heart failure.
回顾抑制癌症和心脏中的细胞外信号调节激酶 1/2（ERK1/2）级联：疾病和健康中的好坏？Angela Clerk *、Shona U Amadi、Samuel J Smith 和 Peter H SugdenSchool of Biological Sciences, University of Reading, Reading RG6 6AS, UK* Correspondence: a.clerk@reading.ac.uk Received：摘要：细胞外信号调节激酶 1 和 2（ERK1/2）是丝裂原活化蛋白激酶的原型，最早是在细胞分裂及其在癌症中的作用的背景下被发现和研究的。ERK1/2被上游激酶MEK1/2（又称MKK1/2）磷酸化和激活，MEK1/2又被RAF激酶（RAF1、BRAF、ARAF）磷酸化和激活，这些激酶又被RAS家族的小G蛋白（HRAS、KRAS、NRAS）激活。该通路的致癌特性催生了高度特异性的抑制剂，这些抑制剂被成功用于治疗癌症，尤其是黑色素瘤。目前临床上使用的抑制剂可抑制 RAS、RAF 激酶和 MEK1/2 的某些异构体，还有更多这些激酶的抑制剂正在临床试验中。抑制 ERK1/2 本身的新药正在进入临床。ERK1/2 级联在心脏中也很重要。它促进心肌细胞肥大和心脏保护，以对抗病理生理压力，并在促进心脏纤维化方面发挥重要作用，对心脏功能造成有害影响。在此，我们总结了 ERK1/2 信号在癌症和心脏中的作用，概述了 ERK1/2 级联抑制剂在癌症治疗中的发展情况，提供了已被批准为癌症治疗药物和正在进行临床试验的药物的信息，并讨论了这些 ERK1/2 级联抑制剂对心脏的已知和预测后果。与此同时，我们还考虑了这些药物是否一定会对心脏造成损害，或者是否/何时可以将其重新用于预防或治疗心衰。
{"title":"Inhibiting the Extracellular Signal-regulated Kinase 1/2 (ERK1/2) Cascade in Cancer and the Heart: for Better or Worse, in Sickness and Health?","authors":"Angela Clerk","doi":"10.53941/ijddp.2024.100006","DOIUrl":"https://doi.org/10.53941/ijddp.2024.100006","url":null,"abstract":"Review\u0000Inhibiting the Extracellular Signal-regulated Kinase 1/2 (ERK1/2) Cascade in Cancer and the Heart: for Better or Worse, in Sickness and Health?\u0000\u0000Angela Clerk *, Shona U Amadi, Samuel J Smith, and Peter H Sugden\u0000\u0000\u0000School of Biological Sciences, University of Reading, Reading RG6 6AS, UK\u0000* Correspondence: a.clerk@reading.ac.uk\u0000 \u0000Received: 3 April 2024; Revised: 27 April 2024; Accepted: 29 April 2024; Published: 23 May 2024\u0000 \u0000Abstract: The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are the prototypic mitogen-activated protein kinases, first discovered and investigated in the context of cell division and their role in cancer. ERK1/2 are phosphorylated and activated by upstream kinases, MEK1/2 (also known as MKK1/2) that are in turn phosphorylated and activated by RAF kinases (RAF1, BRAF, ARAF), these being activated by small G proteins of the RAS family (HRAS, KRAS, NRAS). The oncogenic nature of the pathway has resulted in the generation of highly specific inhibitors that are successfully used to treat cancer, particularly melanoma. Those in clinical use currently inhibit some isoforms of RAS, RAF kinases and MEK1/2, with additional inhibitors of these kinases in clinical trials. New drugs are now entering the clinic to inhibit ERK1/2 themselves. The ERK1/2 cascade is also important in the heart. It promotes cardiomyocyte hypertrophy and cardioprotection to counter pathophysiological stresses, and plays a significant role in enhancing cardiac fibrosis with detrimental consequences for cardiac function. Here, we summarise the role of ERK1/2 signalling in cancer and the heart, we outline the development of ERK1/2 cascade inhibitors for cancer providing information on those that are approved as cancer treatments and those which are in clinical trials, and we discuss the known and predicted consequences of these ERK1/2 cascade inhibitors for the heart. Integral with this, we consider whether these drugs are necessarily detrimental to the heart or if/when they may be repurposed to prevent or treat heart failure.\u0000","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141103480","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 : 2024-03-18DOI: 10.53941/ijddp.2024.100005
Hongyuan Zhang, Minxing Zhao, Yanrong Liu
Review Breaking Boundaries: Novel Effects of Levosimendan in Various Diseases Hongyuan Zhang 1, Minxing Zhao 2, and Yanrong Liu 1,3,* 1 Michael Smith building, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, M139PT Manchester, UK. 2 Loreto High School, Chorlt on, M217SW Manchester, UK. 3 The Department of Cardiology, the 1st Affiliated Nanjing Medical University, 300 Guangzhou Road, Nanjing, China. * Correspondence: yanrong.liu@manchester.ac.uk Received: 6 February 2024 Accepted: 23 February 2024 Published: 18 March 2024 Abstract: Levosimendan, an inodilator that has been applied in clinical use for over two decades, has transcended its initial indication in the management of acutely decompensated chronic heart failure. Over the years, it has been adopted in septic shock, perioperative use of cardiac surgery, advanced end-stage heart failure, and has shown potential for inhaled administration, highlighting its versatility. Levosimendan has diverse mechanisms of action which mediate its non-traditional uses. Ongoing research aims to expand our understanding and develop personalized treatment strategies for the use of levosimendan. The significance of levosimendan in acute decompensated heart failure and cardiogenic shock, highlights its evolving role in contemporary cardiovascular medicine. This comprehensive review explores its pharmacodynamics, effects, and the challenges and opportunities it presents in various clinical settings. We describe levosimedan’s expanding usage, ranging from septic shock, intermittent intravenous in advanced heart failure, perioperative cardiac surgery and pulmonary hypertension management by inhaled levosimendan as well as its future prospects.
回顾突破界限：左西孟旦在多种疾病中的新作用Hongyuan Zhang 1, Minxing Zhao 2, and Yanrong Liu 1,3,*1 Michael Smith building, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, M139PT Manchester, UK.2.Loreto High School, Chorlt on, M217SW Manchester, UK.3 The Department of Cardiology, the 1st Affiliated Nanjing Medical University, 300 Guangzhou Road, Nanjing, China.* Correspondence: yanrong.liu@manchester.ac.uk Received：摘要： 左西孟旦是一种在临床上应用了二十多年的肌注扩张剂，已超越了其最初用于治疗急性失代偿期慢性心力衰竭的适应症。多年来，它已被用于脓毒性休克、心脏手术围手术期、晚期终末期心力衰竭，并显示出吸入给药的潜力，突显了其多功能性。左西孟旦具有多种作用机制，这些机制促成了它的非传统用途。正在进行的研究旨在扩大我们对左西孟旦的了解，并为左西孟旦的使用制定个性化治疗策略。左西孟旦在急性失代偿性心力衰竭和心源性休克中的重要作用凸显了其在当代心血管医学中不断发展的作用。本综述探讨了左西孟旦的药效学、作用及其在各种临床环境中带来的挑战和机遇。我们介绍了左西孟旦不断扩大的应用范围，包括脓毒性休克、晚期心衰的间歇性静脉注射、心脏手术围手术期、吸入左西孟旦治疗肺动脉高压以及其未来前景。
{"title":"Breaking Boundaries: Novel Effects of Levosimendan in Various Diseases","authors":"Hongyuan Zhang, Minxing Zhao, Yanrong Liu","doi":"10.53941/ijddp.2024.100005","DOIUrl":"https://doi.org/10.53941/ijddp.2024.100005","url":null,"abstract":"Review\u0000Breaking Boundaries: Novel Effects of Levosimendan in Various Diseases\u0000\u0000Hongyuan Zhang 1, Minxing Zhao 2, and Yanrong Liu 1,3,*\u00001 Michael Smith building, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, M139PT Manchester, UK.\u00002 Loreto High School, Chorlt on, M217SW Manchester, UK.\u00003 The Department of Cardiology, the 1st Affiliated Nanjing Medical University, 300 Guangzhou Road, Nanjing, China.\u0000* Correspondence: yanrong.liu@manchester.ac.uk\u0000\u0000\u0000 \u0000 \u0000Received: 6 February 2024\u0000Accepted: 23 February 2024\u0000Published: 18 March 2024\u0000 \u0000\u0000Abstract: Levosimendan, an inodilator that has been applied in clinical use for over two decades, has transcended its initial indication in the management of acutely decompensated chronic heart failure. Over the years, it has been adopted in septic shock, perioperative use of cardiac surgery, advanced end-stage heart failure, and has shown potential for inhaled administration, highlighting its versatility. Levosimendan has diverse mechanisms of action which mediate its non-traditional uses. Ongoing research aims to expand our understanding and develop personalized treatment strategies for the use of levosimendan. The significance of levosimendan in acute decompensated heart failure and cardiogenic shock, highlights its evolving role in contemporary cardiovascular medicine. This comprehensive review explores its pharmacodynamics, effects, and the challenges and opportunities it presents in various clinical settings. We describe levosimedan’s expanding usage, ranging from septic shock, intermittent intravenous in advanced heart failure, perioperative cardiac surgery and pulmonary hypertension management by inhaled levosimendan as well as its future prospects.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140233650","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 : 2024-03-18DOI: 10.53941/ijddp.2024.100004
Xu Chen, Xuan Wu, Linyan Li, Xiaoming Zhu
Review Development of Proteasome Inhibitors for Cancer Therapy Xu Chen † , Xuan Wu † , Linyan Li, and Xiaoming Zhu * State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR, 999078, China * Correspondence: xmzhu@must.edu.mo Received: 12 January 2024 Accepted: 19 February 2024 Published: 18 March 2024 Abstract: The ubiquitin proteasome system (UPS) is considered a crucial degradation machinery in cellular processes of protein quality control and homeostasis. Dysregulation of the UPS is closely associated with many diseases. The proteasome is a key core component of the UPS, which can prevent the accumulation of misfolded proteins and regulate various cellular processes such as cell cycle, apoptosis, and immune responses. In the past two decades, a total of three proteasome inhibitors have been approved for the treatment of hematological malignancies, including bortezomib, carfilzomib, and ixazomib. Additionally, accumulating reports have suggested that some natural product-derived proteasome inhibitors have been developed as anti-cancer drug candidates. In this review, we summarize the development of proteasome inhibitors as well as the mechanisms involved, clinical application progress, and drug resistance. The natural products of proteasome inhibitors and their future perspectives will also be discussed.
综述蛋白酶体抑制剂在癌症治疗中的开发陈旭 † ，吴璇 † ，李林燕，朱晓明 *澳门科技大学澳门医药卫生应用研究院中医药质量研究国家重点实验室，中国澳门特别行政区氹仔，999078* 通讯地址：xmzhu@must.edu.mo 收稿日期：2024 年 1 月 12 日收稿日期：2024 年 1 月 12 日12 January 2024Accepted：19 February 2024Published: 18 March 2024 摘要：泛素蛋白酶体系统（UPS）被认为是细胞蛋白质质量控制和平衡过程中的关键降解机制。UPS 的失调与许多疾病密切相关。蛋白酶体是 UPS 的关键核心成分，它可以防止错误折叠蛋白的积累，并调节细胞周期、细胞凋亡和免疫反应等各种细胞过程。在过去二十年中，共有三种蛋白酶体抑制剂被批准用于治疗血液恶性肿瘤，包括硼替佐米、卡非佐米和伊沙佐米。此外，越来越多的报道表明，一些天然产物衍生的蛋白酶体抑制剂已被开发为抗癌候选药物。在这篇综述中，我们总结了蛋白酶体抑制剂的发展、相关机制、临床应用进展和耐药性。此外，还将讨论蛋白酶体抑制剂的天然产物及其未来前景。
{"title":"Development of Proteasome Inhibitors for Cancer Therapy","authors":"Xu Chen, Xuan Wu, Linyan Li, Xiaoming Zhu","doi":"10.53941/ijddp.2024.100004","DOIUrl":"https://doi.org/10.53941/ijddp.2024.100004","url":null,"abstract":"Review\u0000Development of Proteasome Inhibitors for Cancer Therapy\u0000\u0000Xu Chen † , Xuan Wu † , Linyan Li, and Xiaoming Zhu *\u0000\u0000\u0000State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR, 999078, China\u0000* Correspondence: xmzhu@must.edu.mo\u0000 \u0000 \u0000Received: 12 January 2024\u0000Accepted: 19 February 2024\u0000Published: 18 March 2024\u0000 \u0000\u0000Abstract: The ubiquitin proteasome system (UPS) is considered a crucial degradation machinery in cellular processes of protein quality control and homeostasis. Dysregulation of the UPS is closely associated with many diseases. The proteasome is a key core component of the UPS, which can prevent the accumulation of misfolded proteins and regulate various cellular processes such as cell cycle, apoptosis, and immune responses. In the past two decades, a total of three proteasome inhibitors have been approved for the treatment of hematological malignancies, including bortezomib, carfilzomib, and ixazomib. Additionally, accumulating reports have suggested that some natural product-derived proteasome inhibitors have been developed as anti-cancer drug candidates. In this review, we summarize the development of proteasome inhibitors as well as the mechanisms involved, clinical application progress, and drug resistance. The natural products of proteasome inhibitors and their future perspectives will also be discussed.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140233753","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 : 2024-03-06DOI: 10.53941/ijddp.2024.100002
Tayyiba Azam, Hongyuan Zhang, S. Hille, Oliver J. Müller, Elizabeth J. Cartwright, Xin Wang
Article Mkk7 Protects Against Cardiac Dysfunction in Heart Failure with Preserved Ejection Fraction Tayyiba Azam 1, * , Hongyuan Zhang 1, Susanne S. Hille 2, Elizabeth J. Cartwright 1, Oliver J. Müller 2, and Xin Wang 1, * 1 Faculty of Biology, Medicine, and Health, University of Manchester, Oxford Road, M13 9PT, Manchester, UK 2 Department of Internal Medicine III, University of Kiel, Germany; German Centre for Cardiovascular Research (DZHK), 24105 Partner Site Hamburg/Kiel/Lübeck, Germany * Correspondence: xin.wang@manchester.ac.uk (Xin Wang); tayyiba.azam@manchester.ac.uk (Tayyiba Azam) Received: 12 June 2023 Accepted: 25 September 2023 Published: 6 March 2024 Abstract: Shifts in epidemiological patterns foretell a rapid increase in the number of patients with heart failure (HF) globally, representing a significant health and economic burden. Heart failure with preserved ejection (HFpEF) is now considered the prevailing subtype of HF, with no effective treatment available to combat this syndrome. Previous studies have highlighted the cardioprotective role of MKK7 during cardiac pathology, however, no extensive research has been performed to examine MKK7 in the context of HFpEF. This study aimed to address this shortcoming by using adeno-associated virus (AAV) 9 to overexpress MKK7 in the two-hit clinically relevant HFpEF mouse model. We report that cardiomyocyte-specific overexpression of MKK7 improved the HFpEF phenotype in mice, by impeding cardiac diastolic dysfunction and myocardial fibrosis. Mechanistically, it was found that MKK7 ameliorated ER stress by maintaining IRE1-XBP1 signalling and blunted CHOP increase in the myocardium. To summarise, MKK7 overexpression holds the ability to protect the myocardium from HFpEF associated pathologies.
文章Mkk7可保护射血分数保留型心力衰竭患者的心脏功能障碍Tayyiba Azam 1, * , Hongyuan Zhang 1, Susanne S. Hille 2, Elizabeth J. Cartwright 1, Oliver J. Müller 2, and Xin Wang 1, *1 英国曼彻斯特大学生物、医学和健康学院，牛津路，M13 9PT。Müller 2, and Xin Wang 1, *1 Faculty of Biology, Medicine, and Health, University of Manchester, Oxford Road, M13 9PT, Manchester, UK2 Department of Internal Medicine III, University of Kiel, Germany; German Centre for Cardiovascular Research (DZHK), 24105 Partner Site Hamburg/Kiel/Lübeck, Germany* Correspondence: xin.wang@manchester.ac.uk (Xin Wang); tayyiba.azam@manchester.ac.uk (Tayyiba Azam) Received：摘要：流行病学模式的转变预示着全球心力衰竭（HF）患者人数将迅速增加，这将带来巨大的健康和经济负担。保留射血功能的心力衰竭（HFpEF）目前被认为是心力衰竭的主要亚型，目前尚无有效的治疗方法来对抗这种综合征。以往的研究强调了 MKK7 在心脏病理过程中的心脏保护作用，然而，还没有进行过广泛的研究来探讨 MKK7 在 HFpEF 中的作用。本研究旨在通过使用腺相关病毒（AAV）9 在两击临床相关的高频低氧血症小鼠模型中过表达 MKK7 来弥补这一不足。我们报告说，通过抑制心脏舒张功能障碍和心肌纤维化，心肌细胞特异性过表达 MKK7 改善了小鼠的高频心衰表型。从机理上讲，研究发现MKK7通过维持IRE1-XBP1信号传导来改善ER应激，并抑制心肌中CHOP的增加。总之，MKK7 的过表达能够保护心肌免受高频心衰相关病症的影响。
{"title":"Mkk7 Protects Against Cardiac Dysfunction in Heart Failure with Preserved Ejection Fraction","authors":"Tayyiba Azam, Hongyuan Zhang, S. Hille, Oliver J. Müller, Elizabeth J. Cartwright, Xin Wang","doi":"10.53941/ijddp.2024.100002","DOIUrl":"https://doi.org/10.53941/ijddp.2024.100002","url":null,"abstract":"Article\u0000Mkk7 Protects Against Cardiac Dysfunction in Heart Failure with Preserved Ejection Fraction\u0000\u0000Tayyiba Azam 1, * , Hongyuan Zhang 1, Susanne S. Hille 2, Elizabeth J. Cartwright 1, Oliver J. Müller 2, and Xin Wang 1, *\u0000\u0000\u00001 Faculty of Biology, Medicine, and Health, University of Manchester, Oxford Road, M13 9PT, Manchester, UK\u00002 Department of Internal Medicine III, University of Kiel, Germany; German Centre for Cardiovascular Research (DZHK), 24105 Partner Site Hamburg/Kiel/Lübeck, Germany\u0000* Correspondence: xin.wang@manchester.ac.uk (Xin Wang); tayyiba.azam@manchester.ac.uk (Tayyiba Azam)\u0000 \u0000 \u0000Received: 12 June 2023\u0000Accepted: 25 September 2023\u0000Published: 6 March 2024\u0000 \u0000\u0000Abstract: Shifts in epidemiological patterns foretell a rapid increase in the number of patients with heart failure (HF) globally, representing a significant health and economic burden. Heart failure with preserved ejection (HFpEF) is now considered the prevailing subtype of HF, with no effective treatment available to combat this syndrome. Previous studies have highlighted the cardioprotective role of MKK7 during cardiac pathology, however, no extensive research has been performed to examine MKK7 in the context of HFpEF. This study aimed to address this shortcoming by using adeno-associated virus (AAV) 9 to overexpress MKK7 in the two-hit clinically relevant HFpEF mouse model. We report that cardiomyocyte-specific overexpression of MKK7 improved the HFpEF phenotype in mice, by impeding cardiac diastolic dysfunction and myocardial fibrosis. Mechanistically, it was found that MKK7 ameliorated ER stress by maintaining IRE1-XBP1 signalling and blunted CHOP increase in the myocardium. To summarise, MKK7 overexpression holds the ability to protect the myocardium from HFpEF associated pathologies.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140262237","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 : 2024-03-06DOI: 10.53941/ijddp.2024.100003
Zijie Liu, Tianyu Song, Liping Xie
Review Transforming Growth Factor β Signaling Pathway as a Potential Drug Target in Treating Aortic Diseases Zijie Liu 1,2, Tianyu Song 3, and Liping Xie 1,2,3, * 1 Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211166, China 2 School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China 3 Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing 211166, China * Correspondence: lipingxie@njmu.edu.cn Received: 16 October 2023 Accepted: 20 November 2023 Published: 6 March 2024 Abstract: The transforming growth factor β (TGF-β) signaling pathway is crucial for preserving the structural homeostasis of the aorta and promoting aortic development. This pathway encompasses both SMAD-dependent canonical pathway and SMAD-independent non-canonical signaling pathway. Heritable thoracic aortic aneurysms and dissection are highly correlated with genetic alterations in TGF-β canonical signaling-related genes. However, depending on the stage of the disease, the TGF-β signaling pathway can have either inhibitory or aggravation effects, making its roles in aortic disease complex and occasionally contradictory. This review aims to elucidate the biological mechanisms underlying the TGF-β signaling pathway in the most common aortic diseases, namely acute aortic syndromes and aortic aneurysms, and to evaluate the potential clinical application of TGF-β-targeting therapies in aortic diseases.
{"title":"Transforming Growth Factor β Signaling Pathway as a Potential Drug Target in Treating Aortic Diseases","authors":"Zijie Liu, Tianyu Song, Liping Xie","doi":"10.53941/ijddp.2024.100003","DOIUrl":"https://doi.org/10.53941/ijddp.2024.100003","url":null,"abstract":"Review\u0000Transforming Growth Factor β Signaling Pathway as a Potential Drug Target in Treating Aortic Diseases\u0000\u0000Zijie Liu 1,2, Tianyu Song 3, and Liping Xie 1,2,3, *\u0000\u0000\u00001 Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211166, China\u00002 School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China\u00003 Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing 211166, China\u0000* Correspondence: lipingxie@njmu.edu.cn\u0000 \u0000 \u0000Received: 16 October 2023\u0000Accepted: 20 November 2023\u0000Published: 6 March 2024\u0000 \u0000\u0000Abstract: The transforming growth factor β (TGF-β) signaling pathway is crucial for preserving the structural homeostasis of the aorta and promoting aortic development. This pathway encompasses both SMAD-dependent canonical pathway and SMAD-independent non-canonical signaling pathway. Heritable thoracic aortic aneurysms and dissection are highly correlated with genetic alterations in TGF-β canonical signaling-related genes. However, depending on the stage of the disease, the TGF-β signaling pathway can have either inhibitory or aggravation effects, making its roles in aortic disease complex and occasionally contradictory. This review aims to elucidate the biological mechanisms underlying the TGF-β signaling pathway in the most common aortic diseases, namely acute aortic syndromes and aortic aneurysms, and to evaluate the potential clinical application of TGF-β-targeting therapies in aortic diseases.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140262464","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.2023.100006
Yu He, Ming Lei
Expert review p21-Activated Kinases Present a New Drug Target for Hypertrophic Cardiomyopathy He Yu , and Lei Ming , * Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK * Correspondence: ming.lei@pharm.ox.ac.uk Received: 17 February 2023 Accepted: 26 March 2023 Published: 21 August 2023 Abstract: Hypertrophic cardiomyopathy (HCM), primarily involving mutations in sarcomeric proteins, is the most common form of inherited heart disease and a leading cause of sudden death in young adults and athletes. HCM patients present with cardiac hypertrophy, fibrosis, and diastolic dysfunction often in a progressive manner. Despite significant progress made in understanding the molecular genetic basis of HCM, there remains a lack of effective and specific treatment for preventing disease progression in HCM. This article first provides an overview of recent progress in understanding the pathogenic basis of disease progression in HCM, in particular dysfunctional calcium handling, mitochondrial impairment, and endoplasmic reticulum stress. This article then analyses the evidence for critical roles of the multifunctional enzymes P21-activated kinase-1 and 2 (Pak1/2) in the heart and our opinion on their therapeutic value as a promising druggable target in pathological hypertrophy and associated ventricular arrhythmias.
何宇，雷明，*牛津大学药学系，Mansfield Road, Oxford, OX1 3QT, UK *通讯:ming.lei@pharm.ox.ac.uk收稿:2023年2月17日接受:2023年3月26日发表:2023年8月21日肥厚性心肌病(HCM)主要涉及肌瘤蛋白的突变，是最常见的遗传性心脏病，也是年轻人和运动员猝死的主要原因。HCM患者表现为心脏肥厚、纤维化和舒张功能障碍，通常呈进行性。尽管在了解HCM的分子遗传学基础方面取得了重大进展，但仍然缺乏有效和特异性的治疗方法来预防HCM的疾病进展。本文首先概述了HCM疾病进展的致病基础的最新进展，特别是钙处理功能障碍、线粒体损伤和内质网应激。本文分析了多功能酶p21活化激酶-1和激酶- 2 (Pak1/2)在心脏中的关键作用的证据，以及它们作为病理性肥厚和相关室性心律失常的有希望的药物靶点的治疗价值。
{"title":"p21-Activated Kinases Present a New Drug Target for Hypertrophic Cardiomyopathy","authors":"Yu He, Ming Lei","doi":"10.53941/ijddp.2023.100006","DOIUrl":"https://doi.org/10.53941/ijddp.2023.100006","url":null,"abstract":"Expert review p21-Activated Kinases Present a New Drug Target for Hypertrophic Cardiomyopathy He Yu , and Lei Ming , * Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK * Correspondence: ming.lei@pharm.ox.ac.uk Received: 17 February 2023 Accepted: 26 March 2023 Published: 21 August 2023 Abstract: Hypertrophic cardiomyopathy (HCM), primarily involving mutations in sarcomeric proteins, is the most common form of inherited heart disease and a leading cause of sudden death in young adults and athletes. HCM patients present with cardiac hypertrophy, fibrosis, and diastolic dysfunction often in a progressive manner. Despite significant progress made in understanding the molecular genetic basis of HCM, there remains a lack of effective and specific treatment for preventing disease progression in HCM. This article first provides an overview of recent progress in understanding the pathogenic basis of disease progression in HCM, in particular dysfunctional calcium handling, mitochondrial impairment, and endoplasmic reticulum stress. This article then analyses the evidence for critical roles of the multifunctional enzymes P21-activated kinase-1 and 2 (Pak1/2) in the heart and our opinion on their therapeutic value as a promising druggable target in pathological hypertrophy and associated ventricular arrhythmias.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135343348","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}
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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：