Mohan Maradumane L, Vasudevan Neelakantan T, Naga Prasad Sathyamangla V
*Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH; and †Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH.
J Cardiovasc Pharmacol. 2017 Aug;70(2):61-73. doi: 10.1097/FJC.0000000000000456.
Proinflammatory reaction by the body occurs acutely in response to injury that is considered primarily beneficial. However, sustained proinflammatory cytokines observed with chronic pathologies such as metabolic syndrome, cancer, and arthritis are detrimental and in many cases is a major cardiovascular risk factor. Proinflammatory cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor α (TNFα) have long been implicated in cardiovascular risk and considered to be a major underlying cause for heart failure (HF). The failure of the anti-TNFα therapy for HF indicates our elusive understanding on the dichotomous role of proinflammatory cytokines on acutely beneficial effects versus long-term deleterious effects. Despite these well-described observations, less is known about the mechanistic underpinnings of proinflammatory cytokines especially TNFα in pathogenesis of HF. Increasing evidence suggests the existence of an active cross-talk between the TNFα receptor signaling and G-protein-coupled receptors such as β-adrenergic receptor (βAR). Given that βARs are the key regulators of cardiac function, the review will discuss the current state of understanding on the role of proinflammatory cytokine TNFα in regulating βAR function.
身体的促炎反应会在对主要被认为有益的损伤做出反应时急性发生。然而，在诸如代谢综合征、癌症和关节炎等慢性疾病中观察到的持续促炎细胞因子是有害的，并且在许多情况下是主要的心血管危险因素。诸如白细胞介素-1、白细胞介素-6和肿瘤坏死因子α（TNFα）等促炎细胞因子长期以来一直与心血管风险相关，并被认为是心力衰竭（HF）的主要潜在原因。抗TNFα治疗HF的失败表明我们对促炎细胞因子在急性有益作用与长期有害作用方面的二分法作用理解不足。尽管有这些已充分描述的观察结果，但关于促炎细胞因子尤其是TNFα在HF发病机制中的机制基础知之甚少。越来越多的证据表明TNFα受体信号传导与G蛋白偶联受体如β-肾上腺素能受体（βAR）之间存在活跃的相互作用。鉴于βAR是心脏功能的关键调节因子，本综述将讨论目前对促炎细胞因子TNFα在调节βAR功能中作用的理解现状。
