低酸素が誘導する血管平滑筋細胞遊走因子としてのトロンボスポンジン-1の作用機構(誌上シンポジウム)

スポンサーリンク

概要

論文の詳細を見る
When the arterial wall thickens and blood-diffusion capacity is low in atherosclerotic lesions, hypoxia is a key factor for the development of atherosclerosis. Under hypoxic conditions, >100 genes, including those encoding many growth factors, are known to be induced by a transcriptional factor, hypoxia-inducible factor-1α (HIF-1α). In this study, to examine whether HIF-1α-dependent induction of growth factors is associated with the proliferation and migration of vascular cells in atherosclerotic lesions, we studied the role of thrombospondin-1 (TSP-1), which is induced by hypoxia, in the pathogenesis and progression of atherosclerosis in human coronary artery smooth muscle cells (CASMCs). Under hypoxic conditions, expression of HIF-1α increased time-dependently in human CASMCs with a concomitant increase in the proliferation and migration of cells. Under these conditions, the mRNA and protein levels of TSP-1 and the mRNA level of TSP-1 receptor, integrin β_3, were also enhanced. Neutralizing antibody against TSP-1 reduced hypoxia-induced migration, but not proliferation. Similarly, RGD peptide, which binds to integrin β_3, inhibited cell migration under hypoxia. In HIF-1α-knockdown CASMCs, in which expression of HIF-1α and TSP-1 mRNA and proteins is suppressed, hypoxia-induced migration was markedly reduced. In conclusion, hypoxia in atherosclerotic lesions induces TSP-1, which plays important roles in acceleration of the migration of human CASMCs and the progression of atherosclerosis.
2008-03-01

著者

関連論文

もっと見る

スポンサーリンク