PDF(Pubmed)
Abstract：
Diabetic cardiomyopathy (DCM) is a pathophysiological condition triggered by diabetes mellitus (DM), which can lead to heart failure (HF). One of the most important cellular processes associated with DCM is the death of cardiomyocytes. Gasdermin D (GSDMD) plays a key role in mediating pyroptosis, a type of programmed cell death closely associated with inflammasome activation. Recent studies have revealed that pyroptosis is induced during hyperglycemia, which is crucial to the development of DCM. Although the effects of pyroptosis on DCM have been discussed, the relationship between DCM and GSDMD is not fully clarified. Recent studies gave us the impetus for clarifying the meaning of GSDMD in DCM. The purpose of this review is to summarize new and emerging insights, mainly discussing the structures of GSDMD and the mechanism of pore formation, activation pathways, molecular mechanisms of GSDMD-mediated pyroptosis, and the therapeutic potential of GSDMD in DCM. The implications of this review will pave the way for a new therapeutic target in DCM.
摘要：
糖尿病心肌病（DCM）是由糖尿病（DM）引发的病理生理疾病，这可能导致心力衰竭（HF）。与DCM相关的最重要的细胞过程之一是心肌细胞的死亡。GasderminD（GSDMD）在介导焦亡中起关键作用，一种与炎症体激活密切相关的程序性细胞死亡。最近的研究表明，在高血糖期间会引起焦亡，这对DCM的发展至关重要。尽管已经讨论了焦亡对DCM的影响，DCM与GSDMD之间的关系尚未完全阐明。最近的研究为阐明GSDMD在DCM中的含义提供了动力。这篇综述的目的是总结新的和新兴的见解，主要讨论了GSDMD的结构和孔隙形成机理,激活途径，GSDMD介导的焦亡的分子机制，以及GSDMD在DCM中的治疗潜力。这篇综述的意义将为DCM的新治疗靶点铺平道路。
