Additive contribution of microRNA-34a/b/c to human arterial ageing and atherosclerosis

Abstract Background and aims Preclinical data suggest that the ageing-induced miR-34a regulates vascular senescence. Herein we sought to assess whether the miR-34 family members miR-34a, miR-34b and miR-34c are involved in human arterial disease. Methods Expression levels of miR-34a/b/c were quantified by TaqMan assay in peripheral blood mononuclear cells (PBMCs) derived from a consecutive cohort of 221 subjects who underwent cardiovascular risk assessment and thorough vascular examination for aortic stiffness and extent of arterial atherosclerosis. Results High miR-34a was independently associated with the presence of CAD [OR(95%C.I.): 3.87(1.56-9.56); p=0.003] and high miR-34c with the number of diseased arterial beds [OR(95%C.I.): 1.88 (1.034-3.41); p=0.038], while concurrent high expression of miR-34-a/c or all three miR-34a/b/c was associated with aortic stiffening (miR-34a/c: p=0.022; miR-34a/b/c: p=0.041) and with the extent of atherosclerosis [OR(95%C.I.) for number of coronary arteries [miR-34a/c: 3.29 (1.085-9.95); miR-34a/b/c: 6.06(1.74-21.2)] and number of diseased arterial beds [miR-34a/c: 3.51 (1.45-8.52); miR-34a/b/c: 2.89 (1.05-7.92)] after controlling for possible confounders (p Conclusions The present study reveals the clinical significance of the additive role of miR-34a/b/c in vascular ageing and atherosclerotic vascular disease.