Diabetologia ( IF 8.4 ) Pub Date : 2022-01-07 , DOI: 10.1007/s00125-021-05637-7 Kim L Ho 1 , Qutuba G Karwi 1 , David Connolly 1 , Simran Pherwani 1 , Ezra B Ketema 1 , John R Ussher 2 , Gary D Lopaschuk 1
|
Diabetes contributes to the development of heart failure through various metabolic, structural and biochemical changes. The presence of diabetes increases the risk for the development of cardiovascular disease (CVD), and since the introduction of cardiovascular outcome trials to test diabetic drugs, the importance of improving our understanding of the mechanisms by which diabetes increases the risk for heart failure has come under the spotlight. In addition to the coronary vasculature changes that predispose individuals with diabetes to coronary artery disease, diabetes can also lead to cardiac dysfunction independent of ischaemic heart disease. The hyperlipidaemic, hyperglycaemic and insulin resistant state of diabetes contributes to a perturbed energy metabolic milieu, whereby the heart increases its reliance on fatty acids and decreases glucose oxidative rates. In addition to changes in cardiac energy metabolism, extracellular matrix remodelling contributes to the development of cardiac fibrosis, and impairments in calcium handling result in cardiac contractile dysfunction. Lipotoxicity and glucotoxicity also contribute to impairments in vascular function, cardiac contractility, calcium signalling, oxidative stress, cardiac efficiency and lipoapoptosis. Lastly, changes in protein acetylation, protein methylation and DNA methylation contribute to a myriad of gene expression and protein activity changes. Altogether, these changes lead to decreased cardiac efficiency, increased vulnerability to an ischaemic insult and increased risk for the development of heart failure. This review explores the above mechanisms and the way in which they contribute to cardiac dysfunction in diabetes.
Graphical abstract
中文翻译：
糖尿病的代谢、结构和生化变化与心力衰竭的发展
糖尿病通过各种代谢、结构和生化变化导致心力衰竭的发展。糖尿病的存在增加了患心血管疾病 (CVD) 的风险，并且自从引入心血管结果试验来测试糖尿病药物以来，提高我们对糖尿病增加心力衰竭风险机制的理解的重要性已经到来在聚光灯下。除了使糖尿病患者易患冠状动脉疾病的冠状脉管系统变化外，糖尿病还可导致独立于缺血性心脏病的心脏功能障碍。糖尿病的高脂血症、高血糖和胰岛素抵抗状态导致能量代谢环境受到干扰，从而心脏增加了对脂肪酸的依赖并降低了葡萄糖氧化率。除了心脏能量代谢的变化外，细胞外基质重塑有助于心脏纤维化的发展，钙处理受损导致心脏收缩功能障碍。脂毒性和糖毒性也会导致血管功能、心脏收缩性、钙信号传导、氧化应激、心脏效率和脂肪细胞凋亡的损害。最后，蛋白质乙酰化、蛋白质甲基化和 DNA 甲基化的变化导致无数基因表达和蛋白质活性变化。总之，这些变化会导致心脏效率降低、缺血性损伤易感性增加以及发生心力衰竭的风险增加。
京公网安备 11010802027423号