title: Advanced oxidation protein products induce vascular calcification by promoting osteoblastic trans-differentiation of smooth muscle cells via oxidative stress and ERK pathway.
abstract: Vascular calcification is an actively regulated process similar to bone formation. Advanced oxidation protein products (AOPPs) have been demonstrated to be novel markers of oxidant-mediated protein damage. The present study investigated the role of AOPPs in inducing osteoblastic trans-differentiation and calcification of smooth muscle cells in vitro. We found that AOPPs directly increased the calcium deposition and expression of core binding factor-alpha1 (CBF-alpha1) and osteopontin (OPN) and significantly decreased SM-alpha-actin expression in human aortic smooth muscle cells (HASMCs). AOPPs increased intracellular oxidative stress, which was inhibited by vitamin E. Vitamin E also inhibited AOPP-induced calcium content and osteoblast differentiation of HASMCs. Furthermore, the inhibitor of ERK significantly suppressed the effects of AOPPs on calcification and osteoblast marker expression. These findings suggest that AOPPs induce vascular calcification by promoting osteoblast differentiation of smooth muscle cells via oxidative stress and ERK pathway.
authors.affiliation: Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Huaizhou
authors.initials: H
authors.lastname: You
authors.forename: Haichun
authors.initials: H
authors.lastname: Yang
authors.forename: Qiuyu
authors.initials: Q
authors.lastname: Zhu
authors.forename: Mingxin
authors.initials: M
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Xue
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.forename: Shanyan
authors.initials: S
authors.lastname: Lin
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
mesh_terms: D002114:Calcinosis / Q000209:etiology*; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology*; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D014652:Vascular Diseases / Q000209:etiology*
chemical_list: D011506:Proteins; D048049:Extracellular Signal-Regulated MAP Kinases