MicroRNAs (miRNAs) are a family of small, noncoding RNAs that repress gene expression at the post-transcriptional level. Over 700 miRNAs have been identified in the human genome, of which 20% to 30% regulate human protein-coding genes. Functional in vitro studies have shown that miRNAs are critical for endothelial cell gene expression and function. miRNAs were found in atherosclerosis, cardiac hypertrophy, arterial hypertension, coronary artery disease, diabetes, and inflammatory diseases. We review the current knowledge about the role of miRNAs in endothelial cells with emphasis on the regulation of cellular senescence, angiogenesis, and vascular inflammation. It has been shown that miR-34a, miR-217, miR-200, miR-146c, and miR-181a are responsible for the regulation of cell stress and proliferation processes. Proangiogenic factors include miR-130a, miR-210, miR-424, miR-17-92, miR-27-b, let-7f, and miR-217, while miR-221 and miR-222 have antiangiogenic properties. Other known miRNAs, including miR-31, miR17-3p, miR-155, miR-221, miR-222, and miR-126, are important factors in the regulation of vascular inflammation. Studies show that miRNA expression analysis can be used in the diagnosis and treatment of various diseases; however, additional research is needed before it is used in routine clinical setting.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are relatively new pharmacological agents used to normalize glucose level in type 2 diabetes. Recently, GLP-1RAs have been approved for the treatment of obesity to reduce body weight in non-diabetic patients. The extra-pancre-atic effects of GLP-1RAs, as well as their molecular mechanism of action, are still poorly understood. Thus this study was aimed to verify the hypothesis that the mechanism of action of the GLP-1RAs involves mitochondria and that GLP-1RAs administration can improve mitochondrial functions. For this purpose, preadipocytes CHUBS7 were differentiated to mature adipocytes and then stimulated with GLP-1RA, exendin-4 at 100 nM for 24 h. Oxygen consumption rates, mitochondrial membrane potential, intracellular ATP (adenosine triphosphate) level, SIRT1 and SIRT3 gene expression and the histone deacetylases' activity were measured. Exendin-4 was found to uncouple mitochondrial electron transport from ATP synthesis, slightly decreasing mitochondrial membrane potential in mature adipocytes. Routine respiration and uncoupled oxy- gen consumption rates were higher in exendin-4 treated adipocytes than in the non-treated cells. The ATP level remained unchanged. Exendin-4 enhanced SIRT1 and SIRT3 genes expression. Histone deacetylases' activity in the nuclear fraction was not affected by exendin-4, although the activity of class III histone deacetylases was increased. All of the effects on mitochondrial bioenergetics induced by exendin-4 were abolished by addition of glucagon-like peptide 1 receptor antagonist. In conclusion, exendin-4 activates the sirtuin pathway and increases energy expenditure in human adipocytes. Our results suggest another mechanism that may be responsible for body weight reduction observed in patients using GLP-1RAs.

These findings support the hypothesis that increased GIP signaling has a role in chronic low-grade inflammation.

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