| First Author | Liu S | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 29 | Pages | 24739-53 |
| PubMed ID | 22637477 | Mgi Jnum | J:188859 |
| Mgi Id | MGI:5442466 | Doi | 10.1074/jbc.M112.340216 |
| Citation | Liu S, et al. (2012) Smooth muscle-specific expression of calcium-independent phospholipase A2beta (iPLA2beta) participates in the initiation and early progression of vascular inflammation and neointima formation. J Biol Chem 287(29):24739-53 |
| abstractText | Whether group VIA phospholipase A(2) (iPLA(2)beta) is involved in vascular inflammation and neointima formation is largely unknown. Here, we report that iPLA(2)beta expression increases in the vascular tunica media upon carotid artery ligation and that neointima formation is suppressed by genetic deletion of iPLA(2)beta or by inhibiting its activity or expression via perivascular delivery of bromoenol lactone or of antisense oligonucleotides, respectively. To investigate whether smooth muscle-specific iPLA(2)beta is involved in neointima formation, we generated transgenic mice in which iPLA(2)beta is expressed specifically in smooth muscle cells and demonstrate that smooth muscle-specific expression of iPLA(2)beta 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-alpha markedly induce increased expression of IL-6 and TNF-alpha mRNAs, all of which were suppressed by inhibiting iPLA(2)beta 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 iPLA(2)beta protein 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 iPLA(2)beta participates in the initiation and early progression of vascular inflammation and neointima formation and suggest that iPLA(2)beta may represent a novel therapeutic target for preventing cardiovascular diseases. |
