Isoproterenol mechanisms in inducing myocardial fibrosis and its application as an experimental model for the evaluation of therapeutic potential of phytochemicals and pharmaceuticals  

作　　者：Lujain Bader Eddin Mohamed Fizur Nagoor Meeran Niraj Kumar Jha Samer NGoyal Shreesh Ojha 

机构地区：[1]Department of Pharmacology and Therapeutics,College of Medicine and Health Sciences,UAE University,Al Ain,United Arab Emirates [2]School of Bioengineering&Biosciences,Lovely Professional University,Phagwara,India [3]Centre for Global Health Research,Saveetha Medical College,Saveetha Institute of Medical and Technical Sciences,Saveetha University,Chennai,India [4]Shri Vile Parle Kelvani Mandal's Institute of Pharmacy,Dhule,Maharashtra,India [5]Zayed Bin Sultan Center for Health Sciences,United Arab Emirates University,Al Ain,United Arab Emirates

出　　处：《Animal Models and Experimental Medicine》2025年第1期67-91,共25页动物模型与实验医学(英文)

基　　金：United Arab Emirates University,Grant/Award Number:12R104 and 12R121。

摘　　要：Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the th

关 键 词：cardiac fibrosis CATECHOLAMINES experimental models ISOPROTERENOL myocardial fibrosis PHYTOCHEMICALS β-adrenergic receptors 

分 类 号：R54[医药卫生—心血管疾病]