ERK1/2 inhibition reduces vascular calcification by activating miR-126-3p-DKK1/LRP6 pathway.

ABSTRACT: Rationale: Vascular microcalcification increases the risk of rupture of vulnerable atherosclerotic lesions. Inhibition of ERK1/2 reduces atherosclerosis in animal models while its role in vascular calcification and the underlying mechanisms remains incompletely understood. Methods: Levels of activated ERK1/2, DKK1, LRP6 and BMP2 in human calcific aortic valves were determined. ApoE deficient mice received ERK1/2 inhibitor (U0126) treatment, followed by determination of atherosclerosis, calcification and miR-126-3p production. C57BL/6J mice were used to determine the effect of U0126 on Vitamin D₃ (VD₃)-induced medial arterial calcification. HUVECs, HAECs and HASMCs were used to determine the effects of ERK1/2 inhibitor or siRNA on SMC calcification and th

SUBMITTER: Zeng P 

PROVIDER: S-EPMC7738895 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature