Circulating miR-21 and eNOS in subclinical atherosclerosis in patients with hypertension

Abstract

Objectives: The aim of this study is to evaluate the relationship of miR-21, nitric oxide (NOx) and endothelial nitric oxide synthase (eNOS) with subclinical atherosclerosis in carotid arteries by measuring carotid intima media thickness (CIMT) in patients with hypertension and healthy controls.

Design and methods: A total of 28 hypertensive and 28 healthy controls were enrolled. MiR-21 expression was analyzed by quantitative reverse transcription-PCR and NOx, and eNOS levels were measured by ELISA assay. CIMT was evaluated by ultrasonography and CIMT ≥ 0.8 mm was accepted as increased CIMT (iCIMT).

Results: C-reactive protein (CRP) level, plasma miR-21 expression level and CIMT were found to be significantly higher in the hypertension group when compared to the control group (p = 0.009, p = 0.002 and p < 0.001, respectively). NOx and eNOS levels were significantly lower in the hypertension group compared to the control group (p < 0.001, both). MiR-21 level was positively correlated with the clinical systolic blood pressure, clinical diastolic blood pressure, CRP and CIMT. MiR-21 was also negatively correlated with NOx and eNOS. Eighteen patients with hypertension had iCIMT. MiR-21 and CRP levels were significantly higher (p < 0.001 and p = 0.001), whereas NOx and eNOS levels were significantly lower in patients with iCIMT (p < 0.001, both).

Conclusion: The decreased levels of NOx and eNOS found in this study indicate the co-existence of endothelial dysfunction and hypertension once more. In the absence of microalbuminuria, the increased miR-21 expression in patients with iCIMT made us conclude that this miRNA might be involved in the early stages of atherosclerotic process in hypertensive patients.

Keywords: Carotid intima media thickness; endothelial nitric oxide synthase; hypertension; microRNA-21; nitric oxide.