Department of Cardiology, Jinshan Hospital, Fudan University, Shanghai, China; Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Cardiology, Jinshan Hospital, Fudan University, Shanghai, China.
Gene. 2024 Sep 25;923:148563. doi: 10.1016/j.gene.2024.148563. Epub 2024 May 14.
Diabetic cardiomyopathy (DCM) is a special type of cardiovascular disease, termed as a situation of abnormal myocardial structure and function that occurs in diabetic patients. However, the most fundamental mechanisms of DCM have not been fully explicated, and useful targets for the therapeutic strategies still need to be explored.
In the present study, we combined bioinformatics analysis and in vitro experiments throughout the process of DCM. Differentially Expressed Genes (DEGs) analysis was performed and the weighted gene co-expression network analysis (WGCNA) was constructed to determine the crucial genes that were tightly connected to DCM. Additionally, Functional enrichment analysis was conducted to define biological pathways. To identify the specific molecular mechanism, the human cardiomyocyte cell line (AC16) was stimulated by high glucose (HG, 50 mM D-glucose) and used to imitate DCM condition. Then, we tentatively examined the effect of high glucose on cardiomyocytes, the expression levels of crucial genes were further validated by in vitro experiments.
Generally, NPPA, IGFBP5, SERPINE1, and C3 emerged as potential therapeutic targets. Functional enrichment analysis performed by bioinformatics indicated that the pathogenesis of DCM is mainly related to heart muscle contraction and calcium (Ca) release activation. In vitro, we discovered that high glucose treatment induced cardiomyocyte injury and exacerbated mitochondrial dysfunction remarkably.
Our research defined four crucial genes, as well as determined that mitochondrial function impairment compromises calcium homeostasis ultimately resulting in contractile dysfunction is a central contributor to DCM progression. Hopefully, this study will offer more effective biomarkers for DCM diagnosis and treatment.
糖尿病心肌病（DCM）是一种特殊类型的心血管疾病，是指在糖尿病患者中出现心肌结构和功能异常的情况。然而，DCM 的最根本机制尚未完全阐明，仍需要探索有用的治疗策略靶点。
本研究通过糖尿病心肌病的全过程结合生物信息学分析和体外实验。进行差异表达基因（DEG）分析，并构建加权基因共表达网络分析（WGCNA），以确定与 DCM 紧密相关的关键基因。此外，进行功能富集分析以定义生物学途径。为了确定特定的分子机制，用人心肌细胞系（AC16）用高葡萄糖（HG，50mM D-葡萄糖）刺激来模拟 DCM 条件。然后，我们初步研究了高葡萄糖对心肌细胞的影响，通过体外实验进一步验证了关键基因的表达水平。
一般来说，NPPA、IGFBP5、SERPINE1 和 C3 被认为是潜在的治疗靶点。生物信息学进行的功能富集分析表明，DCM 的发病机制主要与心肌收缩和钙（Ca）释放激活有关。在体外，我们发现高葡萄糖处理可诱导心肌细胞损伤并显著加剧线粒体功能障碍。
我们的研究确定了四个关键基因，并确定线粒体功能障碍破坏钙稳态，最终导致收缩功能障碍是 DCM 进展的核心因素。希望这项研究将为 DCM 的诊断和治疗提供更多有效的生物标志物。
