DOI: 10.1002/ame2.12496
Isoproterenol mechanisms in inducing myocardial fibrosis and its application as an experimental model for the evaluation of therapeutic potential of phytochemicals and pharmaceuticals
Lujain Bader Eddin1
Mohamed Fizur Nagoor Meeran1
Niraj Kumar Jha2
Samer N.Goyal3
Shreesh Ojha4
1.Department of Pharmacology and Therapeutics,College of Medicine and Health Sciences,UAE University,Al Ain,United Arab Emirates2.School of Bioengineering & Biosciences,Lovely Professional University,Phagwara,India;Centre for Global Health Research,Saveetha Medical College,Saveetha Institute of Medical and Technical Sciences,Saveetha University,Chennai,India3.Shri Vile Parle Kelvani Mandal's Institute of Pharmacy,Dhule,Maharashtra,India4.Department of Pharmacology and Therapeutics,College of Medicine and Health Sciences,UAE University,Al Ain,United Arab Emirates;Zayed Bin Sultan Center for Health Sciences,United Arab Emirates University,Al Ain,United Arab Emirates
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 nonselective β-adrenergic receptor agonist.The overstimulated and sustained activation of β-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 therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.
机标关键词：applicationevaluationfibrosismodelexperimentalinducingisoproterenolmechanisms
论文发表日期：2025-01-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：25( 67-91 )
英文信息