Diabetic Cardiomyopathy: Unraveling Pathophysiological Mechanisms via Non-coding RNAs

Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus (DM) characterized by changes that result in cardiac remodeling with ventricular dysfunction and eventually heart failure in the absence of other conditions such as arterial hypertension, valvular heart disease, coronary artery disease, and congenital heart disease. DCM develops independently of other cardiovascular risk factors and is associated with metabolic abnormalities, including hyperglycemia and hyperlipidemia. Multiple mechanisms contribute to DCM pathogenesis, such as impaired cardiac insulin signaling, mitochondrial dysfunction, oxidative stress, inflammation, and calcium handling defects. Despite its increasing prevalence, the underlying mechanisms of DCM remain largely unelucidated, and effective treatment is still needed.

Non-coding RNAs (ncRNAs) are transcriptional outputs that do not translate into proteins, exhibiting a diverse range of biogenesis, size, shape, and function. The most extensively studied ncRNAs are microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). It has become a broadly accepted definition that ncRNAs over 200 nucleotides in length are classified as lncRNAs. miRNAs belong to a broader class of ncRNAs known as ‘small RNAs’, which are defined by their size (20–28 nucleotides) and association with Argonaute (Ago) family proteins. Small RNAs act as guides, directing Ago proteins to target nucleic acids to induce gene silencing. miRNAs and lncRNAs regulate various processes involved in DCM, including oxidative stress, inflammation, apoptosis, and autophagy. Therefore, they have been explored as potential biomarkers and therapeutic targets.^,

[…]