MicroRNAs and obesity-induced endothelial dysfunction: key paradigms in molecular therapy

Abstract

The endothelium plays a pivotal role in maintaining vascular health. Obesity is a global epidemic that has seen dramatic increases in both adult and pediatric populations. Obesity perturbs the integrity of normal endothelium, leading to endothelial dysfunction which predisposes the patient to cardiovascular diseases. MicroRNAs (miRNAs) are short, single-stranded, non-coding RNA molecules that play important roles in a variety of cellular processes such as differentiation, proliferation, apoptosis, and stress response; their alteration contributes to the development of many pathologies including obesity. Mediators of obesity-induced endothelial dysfunction include altered endothelial nitric oxide synthase (eNOS), Sirtuin 1 (SIRT1), oxidative stress, autophagy machinery and endoplasmic reticulum (ER) stress. All of these factors have been shown to be either directly or indirectly caused by gene regulatory mechanisms of miRNAs. In this review, we aim to provide a comprehensive description of the therapeutic potential of miRNAs to treat obesity-induced endothelial dysfunction. This may lead to the identification of new targets for interventions that may prevent or delay the development of obesity-related cardiovascular disease.

Regulation of miRNAs by Natural Antioxidants in Cardiovascular Diseases: Focus on SIRT1 and eNOS

“…VSMCs are predominant constituents of blood vessels and dynamic components produced in response to vasoactive stimuli [ 4 ]. Increasing cGMP levels in VSMCs decreases the intracellular concentration of Ca 2+ , causes relaxation of vascular smooth muscle, and, thus, acts as a potent vasodilator [ 53 ]. Under several pathological conditions, active eNOS formation with oxygenase activity and NO production is severely reduced, leading to uncoupling of eNOS.…”

“…Thus, this chapter summarizes recent findings on nine different miRNAs, which are highly related to CVD pathology, and their target genes are involved in ROS modulation, especially focusing on the expression of eNOS, SIRT1, and antioxidant system-related enzymes ( Table 1 ). Although eNOS and SIRT1 expression is not directly targeted, certain miRNAs act as potent regulators of redox homeostasis by targeting antioxidant system-related enzymes, such as SODs [ 53 ].…”

“…A recent report revealed a direct interaction between eNOS and miR-15 and miR-16, which induced posttranscriptional regulation of eNOS expression in endothelial cells [ 107 ]. Based on the results obtained from several studies involving animal experiments and clinical cases, inhibition of miR-15 and miR-16 expression protects against eNOS mRNA degradation and prevents the occurrence of vascular dysfunction [ 53 ]. The upregulation of miR-16 expression in the endothelium reduces eNOS expression levels and its activity, leading to impairment of endothelial recovery and NO production by repressing cell proliferation and migration [ 108 ].…”

MicroRNAs and long non-coding RNAs in the pathophysiological processes of diabetic cardiomyopathy: emerging biomarkers and potential therapeutics

“…Independently of other cardiometabolic risk factors, it dysregulates inflammation-related ncRNAs. It was demonstrated that therapeutic manipulations of inflammation-related ncRNAs expression can potentially treat obesity-induced vascular complication [ 32 , 33 ].…”

Identification of an autophagy-related gene expression signature for colorectal cancer

“…By eliminating these abnormal macromolecular components, autophagy contributes to the maintenance of intracellular homeostasis (Fang et al 2020). Autophagy abnormality participates in the development of many diseases, including immune dysfunction, neurodegenerative disease, chronic disease and tumor (Ait-Aissa et al 2020;Li et al 2020;Zhao and Zhang 2019). However, it still remains controversial what role autophagy plays in tumor (Levy et al 2017;Xu et al 2020).…”