Not all arrestins are created equal: Therapeutic implications of the functional diversity of the β-arrestins in the heart
Not all arrestins are created equal: Therapeutic implications of the functional diversity of the β-arrestins in the heart作者机构：Laboratory for the Study of Neurohormonal Control of the Circulation Department of Pharmaceutical Sciences (Pharmacology) College of PharmacyNova Southeastern University Jackson Memorial Hospital Massachusetts General Hospital
出 版 物：《World Journal of Cardiology》 (世界心脏病学杂志（英文版）（电子版）)
年 卷 期：2019年第11卷第2期
页 面：47-56页
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 1002[医学-临床医学] 100602[医学-中西医结合临床] 10[医学]
基 金：a NSU’s President’s Faculty Research and Development Grant(PFRDG)
主 题：Adverse remodeling β-arrestin Biased signaling Cardiac myocyte Cardiac fibroblast contractility Functional divergence G protein-coupled receptor Heart failure Hormone Myocardial infarction Signal transducer
摘 要：The two ubiquitous, outside the retina, G protein-coupled receptor(GPCR)adapter proteins, β-arrestin-1 and-2(also known as arrestin-2 and-3,respectively), have three major functions in cells: GPCR desensitization, i.e.,receptor decoupling from G-proteins; GPCR internalization via clathrin-coated pits; and signal transduction independently of or in parallel to G-proteins. Bothβ-arrestins are expressed in the heart and regulate a large number of cardiac GPCRs. The latter constitute the single most commonly targeted receptor class by Food and Drug Administration-approved cardiovascular drugs, with about onethird of all currently used in the clinic medications affecting GPCR *** β-arrestin-1 and-2 play important roles in signaling and function of several GPCRs, in particular of adrenergic receptors and angiotensin II type 1 receptors,in cardiac myocytes, they have been a major focus of cardiac biology research in recent years. Perhaps the most significant realization coming out of their studies is that these two GPCR adapter proteins, initially thought of as functionally interchangeable, actually exert diametrically opposite effects in the mammalian myocardium. Specifically, the most abundant of the two β-arrestin-1 exerts overall detrimental effects on the heart, such as negative inotropy and promotion of adverse remodeling post-myocardial infarction(MI). In contrast, β-arrestin-2 is overall beneficial for the myocardium, as it has anti-apoptotic and antiinflammatory effects that result in attenuation of post-MI adverse remodeling,while promoting cardiac contractile function. Thus, design of novel cardiac GPCRligands that preferentially activate β-arrestin-2 over β-arrestin-1 has the potential of generating novel cardiovascular therapeutics for heart failure and other heart diseases.
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