Abstract:
Irisin is a myokine secreted under the influence of physical activity and exposure to low temperatures and through different exogenous stimuli by the cleavage of its precursor, fibronectin type III domain-containing protein 5 (FNDC5). It is mainly known for maintaining of metabolic homeostasis, promoting the browning of white adipose tissue, the thermogenesis process, and glucose homeostasis. Growing experimental evidence suggests the possible central role of irisin in the regulation of cardiometabolic pathophysiological processes. On the other side, hydrogen sulfide (H2S) is well recognized as a pleiotropic gasotransmitter that regulates several homeostatic balances and physiological functions and takes part in the pathogenesis of cardiometabolic diseases. Through the S-persulfidation of cysteine protein residues, H2S is capable of interacting with crucial signaling pathways, exerting beneficial effects in regulating glucose and lipid homeostasis as well. H2S and irisin seem to be intertwined; indeed, recently, H2S was found to regulate irisin secretion by activating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/FNDC5/irisin signaling pathway, and they share several mechanisms of action. Their involvement in metabolic diseases is confirmed by the detection of their lower circulating levels in obese and diabetic subjects. Along with the importance of metabolic disorders, these modulators exert favorable effects against cardiovascular diseases, preventing incidents of hypertension, atherosclerosis, heart failure, myocardial infarction, and ischemia-reperfusion injury. This review, for the first time, aims to explore the role of H2S and irisin and their possible crosstalk in cardiovascular diseases, pointing out the main effects exerted through the common molecular pathways involved.
摘要:
Irisin是一种在身体活动和暴露于低温的影响下通过其前体的裂解通过不同的外源刺激分泌的肌动蛋白,含纤连蛋白III型结构域的蛋白5(FNDC5)。它主要以维持代谢稳态而闻名,促进白色脂肪组织的褐变,产热过程,和葡萄糖稳态。越来越多的实验证据表明,irisin在调节心脏代谢病理生理过程中可能具有重要作用。在另一边,硫化氢(H2S)被公认为是一种多效性气体发射器,可调节多种稳态平衡和生理功能,并参与心脏代谢疾病的发病机理。通过半胱氨酸蛋白残基的S-过硫化,H2S能够与关键的信号通路相互作用,在调节葡萄糖和脂质稳态方面也发挥有益作用。H2S和irisin似乎交织在一起;事实上,最近,发现H2S通过激活过氧化物酶体增殖物激活受体γ辅激活因子1-α(PGC-1α)/FNDC5/irisin信号通路来调节irisin的分泌,他们有几个共同的行动机制。通过在肥胖和糖尿病受试者中检测到它们的较低循环水平来证实它们参与代谢疾病。随着代谢紊乱的重要性,这些调节剂对心血管疾病发挥有利作用,预防高血压事件,动脉粥样硬化,心力衰竭,心肌梗塞,和缺血再灌注损伤。这次审查,第一次,目的探讨H2S和irisin及其可能的串扰在心血管疾病中的作用,指出通过所涉及的常见分子途径发挥的主要作用。