Oxidized phospholipids induce type VIII collagen expression and vascular smooth muscle cell migration

Olga A. Cherepanova, Nataliya A. Pidkovka, Olga F. Sarmento, Tadashi Yoshida, Qiong Gan, Eser Adiguzel, Michelle P. Bendeck, Judith Berliner, Norbert Leitinger, Gary K. Owens

研究成果: Article査読

101 被引用数 (Scopus)


Phenotypic switching of vascular smooth muscle cells (VSMCs) is known to play a critical role in the development of atherosclerosis. However, the factors present within lesions that mediate VSMC phenotypic switching are unclear. Oxidized phospholipids (OxPLs), including 1-palmitoyl-2-(5-oxovaleroyl)-sn- glycero-3-phosphorylcholine (POVPC), are active components of minimally modified low density lipoprotein and have been previously shown to induce multiple proatherogenic events in endothelial cells and macrophages, but their effects on VSMCs have been largely unexplored until recently. We previously showed that OxPLs induced phenotypic switching of VSMCs, including suppression of SMC differentiation marker genes. The goal of the present studies was to test the hypothesis that OxPLs alter extracellular matrix production and VSMC migration. Results showed that POVPC activated expression of several extracellular matrix proteins in VSMC. POVPC increased expression of type VIII collagen α1 chain (Col8a1) mRNA in cultured VSMCs and in vivo in rat carotid arteries by 9-fold and 4-fold, respectively. POVPC-induced activation of Col8a1 gene expression was reduced by small interfering RNA-mediated suppression of Krüppel-like factor 4 (Klf4) and Sp1, and was abolished in Klf4-knockout VSMCs. POVPC increased Klf4 binding to the Col8a1 gene promoter both in vivo in rat carotid arteries and in cultured VSMCs based on chromatin immunoprecipitation assays. Moreover, POVPC-induced VSMC migration was markedly reduced in Klf4- or type VIII collagen-knockout VSMCs. Given evidence that OxPLs are present within atherosclerotic lesions, it is interesting to suggest that OxPL-induced changes in VSMC phenotype may contribute to the pathogenesis of atherosclerosis at least in part through changes in extracellular matrix composition.

ジャーナルCirculation research
出版ステータスPublished - 2009 3月 13

ASJC Scopus subject areas

  • 生理学
  • 循環器および心血管医学


「Oxidized phospholipids induce type VIII collagen expression and vascular smooth muscle cell migration」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。