Department of Translational Medical Sciences, Division of Geriatrics, Federico II University, Via Sergio Pansini, 5, Naples 80131, Italy.
Department of Translational Medical Sciences, Division of Geriatrics, Federico II University, Via Sergio Pansini, 5, Naples 80131, Italy; Istituti Clinici Scientifici Maugeri SpA Società Benefit (ICS Maugeri SpA SB), Telese Terme, Italy.
Heart Fail Clin. 2019 Jul;15(3):409-419. doi: 10.1016/j.hfc.2019.02.009. Epub 2019 Apr 6.
Despite improvements in management and therapeutic approach in the last decades, heart failure is still associated with high mortality rates. The sustained enhancement in the sympathetic nervous system tone, observed in patients with heart failure, causes alteration in β-adrenergic receptor signaling and function. This latter phenomenon is the result of several heart failure-related molecular abnormalities involving adrenergic receptors, G-protein-coupled receptor kinases, and β-arrestins. This article summarizes novel encouraging preclinical strategies to reactivate β-adrenergic receptor signaling in heart failure, including pharmacologic and gene therapy approaches, and attempts to translate acquired notions into the clinical setting.
尽管在过去几十年中管理和治疗方法有所改善,但心力衰竭仍然与高死亡率相关。心力衰竭患者中观察到的交感神经系统张力持续增强,导致β-肾上腺素能受体信号和功能发生改变。这种现象是由涉及肾上腺素能受体、G 蛋白偶联受体激酶和β-arrestin 的几种与心力衰竭相关的分子异常引起的。本文总结了新型令人鼓舞的心力衰竭中重新激活β-肾上腺素能受体信号的临床前策略,包括药物和基因治疗方法,并尝试将获得的概念转化为临床环境。