Department of Physiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China.
J Mol Med (Berl). 2019 Jul;97(7):897-907. doi: 10.1007/s00109-019-01790-0. Epub 2019 May 6.
Response to stressors in our environment and daily lives is an adaptation conserved through evolution as it is beneficial in enhancing the survival and continuity of humans. Although stressors have evolved, the drastic physiological response they elicit still remains unchanged. The chronic secretion and circulation of catecholamines to produce physical responses when they are not required may result in pathological consequences which affect cardiac function drastically. This review seeks to point out the probable implication of chronic stress in inducing an inflammation disorder in the heart. We discussed the likely synergy of a G protein-independent stimuli signaling via β-adrenergic receptors in both cardiomyocytes and immune cells during chronic catecholamine stress. To explain this synergy, we hypothesized the possibility of adenylyl cyclases having a regulatory effect on G protein-coupled receptor kinases. This was based on the negative correlations they exhibit during normal cardiac function and heart failures. As such, the downregulation of adenylyl cyclases in cardiomyocytes and immune cells during chronic catecholamine stress enhances the expressions of G protein-coupled receptor kinases. In addition, we explain the maladaptive roles played by G protein-coupled receptor kinase and extracellular signal-regulated kinase in the synergistic cascade that pathologically remodels the heart. Finally, we highlighted the therapeutic potentials of an adenylyl cyclases stimulator to attenuate pathological cardiac hypertrophy (PCH) and improve cardiac function in patients developing cardiac disorders due to chronic catecholamine stress.
应对环境和日常生活中的压力源是一种通过进化而保守下来的适应能力，因为它有利于增强人类的生存和延续。尽管压力源已经进化，但它们引起的剧烈生理反应仍然没有改变。儿茶酚胺的慢性分泌和循环会在不需要时产生生理反应，可能导致严重影响心脏功能的病理后果。这篇综述旨在指出慢性应激在诱导心脏炎症紊乱中的可能作用。我们讨论了在慢性儿茶酚胺应激期间，β肾上腺素能受体在心肌细胞和免疫细胞中通过 G 蛋白非依赖性刺激信号传递的可能协同作用。为了解释这种协同作用，我们假设腺苷酸环化酶对 G 蛋白偶联受体激酶可能具有调节作用。这是基于它们在正常心脏功能和心力衰竭期间表现出的负相关关系。因此，在慢性儿茶酚胺应激期间，心肌细胞和免疫细胞中腺苷酸环化酶的下调增强了 G 蛋白偶联受体激酶的表达。此外，我们解释了 G 蛋白偶联受体激酶和细胞外信号调节激酶在病理重塑心脏的协同级联反应中所起的适应不良作用。最后，我们强调了腺苷酸环化酶刺激剂在减轻由于慢性儿茶酚胺应激导致心脏疾病患者病理性心肌肥厚（PCH）和改善心脏功能方面的治疗潜力。
