Long Non-coding RNA: A Key Regulator in the Pathogenesis of Diabetic Cardiomyopathy

Abstract

In recent years, diabetes mellitus has become a global issue with increasing incidence rate worldwide. Diabetic cardiomyopathy (DCM), one of the important complications of diabetes, refers to patients with type 1 and type 2 diabetes who have ventricular hypertrophy, fibrosis and even diastolic dysfunction. The pathogenesis of DCM is related to oxidative stress, inflammatory response, apoptosis, autophagy, myocardial fibrosis and, diabetic microangiopathy. Long non-coding RNAs (lncRNA) is a non-coding RNA with a length longer than 200 nucleotides which lack the ability of protein coding. With the development of molecular technology, massive evidence demonstrates that lncRNA play a critical role in the molecular mechanism of DCM. Moreover, it can also be used as potential diagnostic markers for DCM. In this review, we intend to summarize the pathological roles and molecular mechanism of lncRNA in the progression of diabetic cardiomyopathy, which may provide promising diagnosis and treatment strategies for DCM.

Keywords: diabetes mellilus; diabetic cardiomyopathy; fibrosis; hypertrophy; long non-coding RNA.

Figure 1

Pathogenesis of diabetic cardiomyopathy. In diabetes mellitus, insulin resistance, hyperglycemia and hyperinsulinemia can cause cardiac insulin resistance and metabolic disorders that induce microvascular dysfunction, Oxidative stress, inflammation, autonomic neuropathy, AGEs, endoplasmic, activated RAAS, mitochondria dysfunction, as well as impaired Ca²⁺ handling. These pathophysiological abnormalities together lead to cardiac fibrosis and hypertrophy, cardiomyocyte death, and dysfunction of coronary microcirculation. Finally, these pathogenic changes in the myocardium impair the diastolic and systolic function of the heart and result in heart failure.

Figure 2

The major function of LncRNAs. (A) LncRNA acts as protein scaffolds and regulates protein function. (B) LncRNA acts as competitive endogenous RNA to interact with miRNAs. (C) LncRNA serves host genes to promote the generation of miRNA. (D) LncRNA serves as a guide to promote the transcriptional regulation via tethering transcription factors (TF) to the promoter region. (E) LncRNA serves as decoys to inhibit gene expression via interacting with TF.