A new perspective on the pleiotropic blood pressure improvement effect of sitagliptin: downregulation of miRNA-155 and miRNA-21

• Published in: Bratislavské lékarské listy Vol. 122; no. 12; pp. 892 - 899
• Main Authors: Gul-Kahraman, M Yilmaz-Bozoglan K, Serhatlioglu, I, Onalan, E, Akkopru, M C, Sahna, E
• Format: Journal Article
• Language: English
• Published: Slovakia 2021
• Subjects: Animals; Blood Pressure; Down-Regulation; Male; MicroRNAs - genetics; NG-Nitroarginine Methyl Ester; Rats; Sitagliptin Phosphate - pharmacology; inflammation; endothelial dysfunction; miRNA-155; sitagliptin blood pressure; miRNA-21
• ISSN: 0006-9248
• DOI: 10.4149/BLL_2021_145

Deterioration of vascular responses is the crucial event in the initiation of cardiovascular problems in hypertension (HT) and diabetes mellitus (DM). A well-known oral antidiabetic, sitagliptin, has pleiotropic effects besides improving glycemic state in type-2 DM. This study aimed to investigate the therapeutic effect of sitagliptin on blood pressure with previously unassessed parameters of well-known pathophysiological processes and especially at the microRNA (miRNA) level where there are many unknowns. N-nitro-L-arginine methyl ester (L-NAME)-induced HT model was performed on nondiabetic male rats. Four groups (including 7 rats in each) were formed: normotensives, sitagliptin-treated, HT and sitagliptin-treated HT. Asymmetric dimethylarginine (ADMA), intercellular adhesion molecule-1 (ICAM-1) and tyrosine hydroxylase (TH), HT related miRNAs were evaluated. In-vitro vessel responses were observed. L-NAME led to a significant increase in blood pressure. Hypertensives exhibited significantly increased contractile responses, consistent with increased ADMA, ICAM-1. Sitagliptin decreased TH levels but not statistically significantly. The new side of the study was the miRNA-21 and miRNA-155 expressions were in line with other parameters in both the HT and sitagliptin-treated HT groups. Sitagliptin may control comorbidities, especially HT and introduces new targets to alleviate vascular responses. The new knowledge is; sitagliptin may show these effects through microRNAs (Tab. 2, Fig. 6, Ref. 46).