Selective deletion of endothelial cell calpain in mice reduces diabetic cardiomyopathy by improving angiogenesis.

摘要: The role of non-cardiomyocytes in diabetic cardiomyopathy has not been fully addressed. This study investigated whether endothelial cell calpain plays a myocardial injury and microvascular rarefaction diabetes, thereby contributing to cardiomyopathy. Endothelial cell-specific Capns1-knockout (KO) mice were generated. Conditions mimicking prediabetes type 1 2 diabetes induced these KO their wild-type littermates. Myocardial function coronary flow reserve assessed by echocardiography. Histological analyses performed determine capillary density, cardiomyocyte size fibrosis the heart. Isolated aortas assayed for neovascularisation. Cultured cardiac cells stimulated with high palmitate. Angiogenesis apoptosis analysed. deletion Capns1 disrupted cells, reduced hypertrophy, alleviated dysfunction mouse models without significantly affecting systemic metabolic variables. These protective effects disruption associated an increase density (wild-type vs Capns1-KO 3646.14 ± 423.51 4708.7 ± 417.93 number/high-power field prediabetes, 2999.36 ± 854.77 4579.22 ± 672.56 2364.87 ± 249.57 3014.63 ± 215.46 diabetes) reserve. Ex vivo analysis neovascularisation revealed more sprouts from aortic rings prediabetic compared In cultured inhibition improved angiogenesis prevented under stress. Mechanistically, elevated protein levels β-catenin constitutive activity suppressed expression cells. Upregulation promoted inhibited whereas knockdown offset results delineate primary inducing impairing via suppression β-catenin, promoting cardiomyopathy, indicate that is promising therapeutic target prevent complications.