The importance of caveolin as a target in the prevention and treatment of diabetic cardiomyopathy

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  Figure 1. Overview of pathological mechanisms underlying diabetic cardiomyopathy and heart failure in diabetic mellitus Pathological stresses such as hyperglycemia, hyperinsulinemia and increased insulin resistance induce endothelial dysfunction through suppression of eNOS and nitric oxide (NO) production, causing impairments in insulin signaling which could further damage the integrity of endothelial tissues. And, reciprocal relationships exist between insulin resistance and endothelial dysfunction. Moreover, these instigators also alter metabolism by reducing GLUT4 expression, increasing AGEs and FFA production. All of which lead to glucotoxicity and lipotoxicity. Meanwhile, ER stress and impaired Ca2+ handling also occur, along with mitochondrial dysfunction and oxidative stress. These, together, cause myocardial hypertrophy, fibrosis, apoptosis and inflammation, contributing to the formation of diabetic cardiomyopathy (DCM) which may proceed to heart failure (HF). However, it is also important to point out that diabetic patients may often have other comorbidities including but not limited to hypertension, obesity, cardiomyopathy and coronary artery diseases that may result in HF. NO,…

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  Figure 2. Signaling pathways involved in the development of diabetic cardiomyopathy. Diabetes is characterized by hyperglycemia, insulin resistance, and increased circulating free fatty acids, which lead to impaired diabetes signaling, increased inflammation, altered Ca2+ handling, and myocardial ischemia, exacerbating the progress of diabetic cardiomyopathy. AGEs, advanced end glycation products; SERCA, sarcoplasmic reticulum Ca2+-ATPase; NO, nitrogen oxide; IRS-1, insulin receptor substrate-1; PI3K, phosphoinositide 3-kinase; MAPK, mitogen-activated protein kinase; GSK-3β, glycogen synthase kinase-3β; PKC, protein kinase C; NF-κB, nuclear factor κB; PPARα, peroxisome proliferator-activated receptor alpha; DAGs, diacylglycerols; CERs, ceramides.