Page 18 - Y. Vascular biology

[Y. Vascular biology-10]

NF-kB-responsive microRNA-155 induces functional

impairment of VSMCs by downregulating soluble guanylyl

cyclase

Minsik Park¹, Wonjin Park¹, Suji Kim¹, Taesam Kim¹, Young-Guen Kwon², Young-Myeong Kim¹

¹Departments of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University,

Chuncheon 24341, South Korea, ²Department of Biochemistry, College of Life Science and Biotechnology, Yonsei
University, Seoul 03722, South Korea

VSMCs play an important role in maintaining vascular function. Inflammation-mediated VSMC dysfunction leads to

atherosclerotic intimal hyperplasia and preeclamptic hypertension. We analyzed the expression levels of miR-155 in
cultured VSMCs, mouse vessels, and clinical specimens, and then assessed its role in VSMC function. Treatment with

TNF-α elevated miR-155 biogenesis in cultured VSMCs and vessel segments, which was prevented by NF-kB
inhibition. MiR-155 expression was also increased in high fat diet-fed ApoE-/- mice and in patients with

atherosclerosis and preeclampsia. MiR-155 levels were inversely correlated with sGCβ1 expression and NO-
dependent cGMP production through targeting of the sGCβ1 transcript. TNF-α-induced miR-155 caused VSMC

phenotypic switching, as confirmed by the downregulation of VSMC-specific marker genes, suppression of cell
proliferation and migration, alterations in cell morphology, and NO-induced vasorelaxation. Moreover, TNF-α did

not cause VSMC phenotypic modulation and limit NO-induced vasodilation in aortic vessels of miR-155-/- mice.
These findings suggest that NF-kB-induced miR-155 impairs the VSMC contractile phenotype and NO-mediated

vasorelaxation by downregulating sGCβ1 expression in atherosclerosis and preeclampsia.