Is β-Arrestin 2 a Magic Bullet for Heart Failure Treatment?
See related article, pp 972–981
Heart failure (HF) is a clinical syndrome that is the terminal stage for several cardiac conditions, such as hypertension, ischemic heart disease, and valvular heart disease. According to the National Health and Nutrition Examination Survey, ≈6.5 million Americans ≥20 years of age live with HF. The prevalence of HF is expected to increase by ≈50% by 2030, resulting in >8 million Americans with HF.1 Mortality and morbidity rates associated with HF place a considerable burden on the healthcare system by being the second most prevalent cause of hospitalization.2 Hemodynamically, HF is defined as a failure of the heart to pump blood in the amounts that meet the metabolic needs of the body. Several mechanisms contribute to the development of HF2: (1) neurohumoral activation, (2) increased myocardial fibrosis, (3) cellular hypertrophy and susceptibility to cell death, (4) vicious circle of adrenergic stimulation that raises myocardial contractility in the setting of increased afterload, (5) abnormal Ca2+ cycling because of Ca2+ leak via ryanodine receptor 2 receptors and lowered SERCa2 (sarco-endoplasmic reticulum Ca2+-ATPase) activity. The article in the current issue of the journal by McCrink et al3 provides an interesting and unexpected insight in the role of β-arrestin 2 in the last 2 mechanisms of HF (β-adrenergic stimulation and regulation of SERCa2 activity) and presents a new treatment option for HF.
β-Adrenergic Stimulation, β-Arrestins, and Ca2+ Cycling in Normal Heart and HF
In normal cardiomyocytes, adrenergic stimulation via β1-adrenergic receptor (β1-AR) and stimulatory G-protein activates protein kinase A, which acts on multiple phosphorylation targets leading to increases in Ca2+ influx via L-type Ca2+ channels, Ca2+ release via ryanodine receptor …