Advances in diabetic cardiomyopathy: current and potential management strategies and emerging biomarkers

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  Figure 1.. Insulin resistance in type 2 diabetes mellitus causes elevated blood sugar levels, increased levels of lipids in the blood, and the accumulation of toxic fat. The overproduction of advanced glycation end products (AGEs) and angiotensin II (Ang II) leads to metabolic alterations in the heart, resulting in mitochondrial dysfunction in cardiomyocytes and endothelial cells. The multiple effects of Ang II are facilitated by type 1 and type 2 Ang II receptors, which interact with different signaling molecules, such as NADPH oxidase, to stimulate the production of reactive oxygen species (ROS) or reactive nitrogen species. Malfunctioning mitochondria generate an excessive amount of reactive oxygen species (ROS), leading to an elevation in oxidative stress. Cell metabolism that deviates from the normal and the presence of oxidative stress can initiate endoplasmic reticulum (ER) stress, leading to the death and enlargement of heart muscle cells, damage to endothelial cells, malfunction in small blood vessels, and the activation of fibroblasts and inflammatory cells that promote the formation of scar tissue. The pathogenic processes of oxidative stress, ER stress, and inflammation can…

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  Figure 2.. The pathway mechanisms for cardiomyocyte damage in DCIM. A decrease in nitric oxide (NO) production from coronary vessels leads to elevated intracellular Ca2+ levels, contributing to contractile dysfunction in the heart. Additionally, excessive fatty acid uptake induces lipotoxicity, which alters lipid membrane composition, myocardial fibrosis and damages mitochondria. This mitochondrial dysfunction results in increased reactive oxygen species (ROS) production, which elevates endoplasmic reticulum (ER) stress, ultimately leading to myocardial cell death.

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  Figure 3.. Pri-miRNAs are transcribed within the nucleus by RNA Pol II. Pre-miRNAs are produced by the process of cleavage mediated by the RNase III enzyme. The pre-miRNAs are conveyed to the cytoplasm via Exportin, fragmented by Dicer to produce double stranded miRNAs, and then transformed into single stranded mature miRNAs. Mature microRNAs (miRNAs) are integrated into the microRNA-induced silencing complex (miRISC), which serves as the functional machinery for directing miRNAs to specific messenger RNAs (mRNAs) and subsequently decreasing gene expression by either degrading the mRNA or inhibiting its translation.