Kar Sumit, Kambis Tyler N, Mishra Paras K
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center , Omaha, Nebraska.
Department of Anesthesiology, University of Nebraska Medical Center , Omaha, Nebraska.
Am J Physiol Heart Circ Physiol. 2019 Jun 1;316(6):H1237-H1252. doi: 10.1152/ajpheart.00004.2019. Epub 2019 Mar 29.
The death of cardiomyocytes is a precursor for the cascade of hypertrophic and fibrotic remodeling that leads to cardiomyopathy. In diabetes mellitus (DM), the metabolic environment of hyperglycemia, hyperlipidemia, and oxidative stress causes cardiomyocyte cell death, leading to diabetic cardiomyopathy (DMCM), an independent cause of heart failure. Understanding the roles of the cell death signaling pathways involved in the development of cardiomyopathies is crucial to the discovery of novel targeted therapeutics and biomarkers for DMCM. Recent evidence suggests that hydrogen sulfide (HS), an endogenous gaseous molecule, has cardioprotective effects against cell death. However, very little is known about signaling by which HS and its downstream targets regulate myocardial cell death in the DM heart. This review focuses on HS in the signaling of apoptotic, autophagic, necroptotic, and pyroptotic cell death in DMCM and other cardiomyopathies, abnormalities in HS synthesis in DM, and potential HS-based therapeutic strategies to mitigate myocardial cell death to ameliorate DMCM.
心肌细胞死亡是导致心肌病的肥厚性和纤维化重塑级联反应的先兆。在糖尿病（DM）中，高血糖、高血脂和氧化应激的代谢环境会导致心肌细胞死亡，进而引发糖尿病性心肌病（DMCM），这是心力衰竭的一个独立病因。了解参与心肌病发展的细胞死亡信号通路的作用对于发现针对DMCM的新型靶向治疗方法和生物标志物至关重要。最近的证据表明，硫化氢（HS）作为一种内源性气体分子，对细胞死亡具有心脏保护作用。然而，关于HS及其下游靶点调节糖尿病心脏中心肌细胞死亡的信号传导，我们知之甚少。本综述重点关注HS在DMCM和其他心肌病中凋亡、自噬、坏死性凋亡和焦亡细胞死亡信号传导中的作用、糖尿病中HS合成的异常情况，以及基于HS减轻心肌细胞死亡以改善DMCM的潜在治疗策略。
