| First Author | Sun J | Year | 2011 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 31 |
| Issue | 11 | Pages | 2500-8 |
| PubMed ID | 21868704 | Mgi Jnum | J:191463 |
| Mgi Id | MGI:5461787 | Doi | 10.1161/ATVBAHA.111.230201 |
| Citation | Sun J, et al. (2011) Cathepsin L activity is essential to elastase perfusion-induced abdominal aortic aneurysms in mice. Arterioscler Thromb Vasc Biol 31(11):2500-8 |
| abstractText | OBJECTIVE: The development of abdominal aortic aneurysms (AAA) requires extensive aortic wall matrix degradation. Human AAA lesions express high levels of cathepsin L (CatL), one of the most potent mammalian elastases. Whether this protease participates directly in AAA pathogenesis, however, is unknown. METHODS AND RESULTS: We generated experimental AAA with aortic elastase perfusion in mice and established an essential role of CatL in AAA formation. After 14 days postperfusion, most wild-type (Ctsl(+/+)) mice developed AAA, but none of the CatL-deficient (Ctsl(-/-)) mice did. AAA lesion macrophage contents, CD4(+) T cell numbers, CD31(+) and laminin-5 angiogenic fragment gamma2(+) microvessel numbers, and elastin fragmentation were all significantly lower in Ctsl(-/-) mice than in Ctsl(+/+) mice. While lesions from Ctsl(-/-) mice contained fewer Ki67(+) proliferating cells than did Ctsl(+/+) mice, the absence of CatL did not affect lesion apoptotic cell contents or medial smooth-muscle cell loss significantly. Mechanistic studies indicated that the absence of CatL reduced lesion chemokine monocyte chemotactic protein-1 content, macrophage and T-cell in vitro transmigration, and angiogenesis, and altered the expression and activities of matrix metalloproteinases and other cysteinyl cathepsins in inflammatory cells, vascular cells, and AAA lesions. CONCLUSION: CatL contributes to AAA formation by promoting lesion inflammatory cell accumulation, angiogenesis, and protease expression. |
