Smooth muscle-specific expression of calcium-independent phospholipase A2β (iPLA2β) participates in the initiation and early progression of vascular inflammation and neointima formation

Shu Liu, Zhongwen Xie, Qingwei Zhao, Huan Pang, John Turk, Lindsay Calderon, Wen Su, Guogang Zhao, Haifei Xu, Ming C. Gong, Zhenheng Guo

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15 Scopus citations

Abstract

Whether group VIA phospholipase A2 (iPLA2β) is involved in vascular inflammation and neointima formation is largely unknown. Here, we report that iPLA2β expression increases in the vascular tunica media upon carotid artery ligation and that neointima formation is suppressed by genetic deletion of iPLA2β or by inhibiting its activity or expression via perivascular delivery of bromoenol lactone or of antisense oligonucleotides, respectively. To investigate whether smooth muscle-specific iPLA2β is involved in neointima formation, we generated transgenic mice in which iPLA2β is expressed specifically in smooth muscle cells and demonstrate that smooth muscle-specific expression of iPLA2β exacerbates ligation-induced neointima formation and enhanced both production of proinflammatory cytokines and vascular infiltration by macrophages. With cultured vascular smooth muscle cell, angiotensin II, arachidonic acid, and TNF-α markedly induce increased expression of IL-6 and TNF-α mRNAs, all of which were suppressed by inhibiting iPLA2β activity or expression with bromoenol lactone, antisense oligonucleotides, and genetic deletion, respectively. Similar suppression also results from genetic deletion of 12/15-lipoxygenase or inhibiting its activity with nordihydroguaiaretic acid or luteolin. Expression of iPLA2βprotein in cultured vascular smooth muscle cells was found to depend on the phenotypic state and to rise upon incubation with TNF-&alpha. Our studies thus illustrate that smooth muscle cell-specific iPLA2α participates in the initiation and early progression of vascular inflammation and neointima formation and suggest that iPLA 2α may represent a novel therapeutic target for preventing cardiovascular diseases.

Original languageEnglish (US)
Pages (from-to)24739-24753
Number of pages15
JournalJournal of Biological Chemistry
Volume287
Issue number29
DOIs
Publication statusPublished - Jul 13 2012

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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