International journal of drug discovery and pharmacology最新文献

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}