Abdominal Aortic Aneurysm formation requires Protein Kinase C‐delta mediated apoptosis and MCP‐1 production

Abdominal Aortic Aneurysm (AAA) is a potentially lethal disease characterized by elastin degradation, smooth muscle depletion, and inflammatory infiltration. We have shown Protein Kinase C‐delta (PKCδ), an important apoptotic mediator, to be upregulated in aneurismal tissues. Thus, we hypothesized that PKC δ participates in the pathogenesis of AAA . Using the common CaCl2 AAA model, we showed PKCδ gene deficiency protected mice from developing aneurysm (aortic expansion 1.13 vs. 1.79, p<0.01, n = 5). This aneurysm‐resistant phenotype was reversed by local restoration of PKCδ expression in the aortic wall (Cont. 1.29 vs. PKCd 2.15, p<0.05, n=3). Conversely, overexpression of a kinase‐dead PKCδ (PKCδ‐DN) in the aorta of PKCδ+/+ mice diminished aneurysm expansion from 2.37 to 1.63 (p<0.05, n=3). Histological analyses consistently showed a link between PKCδ expression and MCP‐1 production. Administration of recombinant MCP‐1 protein to the arterial wall of PKCδ−/− mice restored inflammatory infiltration, elastin degradation, and aortic expansion to a level comparable to what was seen in the PKCδ+/+ mice. In conclusion, PKCδ in the aortic wall is necessary for AAA development and therefore may serve as a potential therapeutic target.