HGF/c-Met signalling promotes Notch3 activation and human vascular smooth muscle cell osteogenic differentiation in vitro

Yiwen Liu, Tao Wang, Jianyun Yan, Naomi Jiagbogu, Daniëlle A M Heideman, Ann E. Canfield, M. Yvonne Alexander

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Objectives: Vascular calcification is a major clinical problem and elucidating the underlying mechanism is important to improve the prognosis of patients with cardiovascular disease. We aimed to elucidate the role and mechanism of action of Hepatocyte Growth Factor (HGF)/c-Met signalling in vascular calcification and establish whether blocking this pathway could prevent mineralisation of vascular smooth muscle cells (VSMCs) in vitro. Methods and results: We demonstrate increased HGF secretion and c-Met up-regulation and phosphorylation during VSMC osteogenic differentiation. Adenoviral-mediated over-expression of HGF (AdHGF) in VSMCs accelerated mineralisation, shown by alizarin red staining, and significantly increased 45Calcium incorporation (1.96±0.54-fold [P
    Original languageEnglish
    Pages (from-to)440-447
    Number of pages7
    JournalAtherosclerosis
    Volume219
    Issue number2
    DOIs
    Publication statusPublished - Dec 2011

    Keywords

    • C-Met
    • Calcification
    • Hepatocyte growth factor
    • NK4
    • Notch signalling
    • Vascular smooth muscle cells

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