| First Author | Morgan S | Year | 2012 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 32 |
| Issue | 10 | Pages | 2493-502 |
| PubMed ID | 22879584 | Mgi Jnum | J:207882 |
| Mgi Id | MGI:5559846 | Doi | 10.1161/ATVBAHA.112.255661 |
| Citation | Morgan S, et al. (2012) Elevated protein kinase C-delta contributes to aneurysm pathogenesis through stimulation of apoptosis and inflammatory signaling. Arterioscler Thromb Vasc Biol 32(10):2493-502 |
| abstractText | OBJECTIVE: Apoptosis of smooth muscle cells (SMCs) is a prominent pathological characteristic of abdominal aortic aneurysm (AAA). We have previously shown that SMC apoptosis stimulates proinflammatory signaling in a mouse model of AAA. Here, we test whether protein kinase C-delta (PKCdelta), an apoptotic mediator, participates in the pathogenesis of AAA by regulating apoptosis and proinflammatory signals. METHODS AND RESULTS: Mouse experimental AAA is induced by perivascular administration of CaCl(2). Mice deficient in PKCdelta exhibit a profound reduction in aneurysmal expansion, SMC apoptosis, and transmural inflammation as compared with wild-type littermates. Delivery of PKCdelta to the aortic wall of PKCdelta(-/-) mice restores aneurysm, whereas overexpression of a dominant negative PKCdelta mutant in the aorta of wild-type mice attenuates aneurysm. In vitro, PKCdelta(-/-) aortic SMCs exhibit significantly impaired monocyte chemoattractant protein-1 production. Ectopic administration of recombinant monocyte chemoattractant protein-1 to the arterial wall of PKCdelta(-/-) mice restores inflammatory response and aneurysm development. CONCLUSIONS: PKCdelta is an important signaling mediator for SMC apoptosis and inflammation in a mouse model of AAA. By stimulating monocyte chemoattractant protein-1 expression in aortic SMCs, upregulated PKCdelta exacerbates the inflammatory process, in turn perpetuating elastin degradation and aneurysmal dilatation. Inhibition of PKCdelta may serve as a potential therapeutic strategy for AAA. |
