Cathepsin K deficiency reduces elastase perfusion-induced abdominal aortic aneurysms in mice

Jiusong Sun, Galina K. Sukhova, Jie Zhang, Han Chen, Sara Sjöberg, Peter Libby, Mingcan Xia, Na Xiong, Bruce D. Gelb, Guo Ping Shi

Producción científica: Articlerevisión exhaustiva

90 Citas (Scopus)

Resumen

Objective-: Cathepsin K (CatK) is one of the most potent mammalian elastases. We have previously shown increased expression of CatK in human abdominal aortic aneurysm (AAA) lesions. Whether this protease participates directly in AAA formation, however, remains unknown. Methods and Results-: Mouse experimental AAA was induced with aortic perfusion of a porcine pancreatic elastase. Using this experimental model, we demonstrated that absence of CatK prevented AAA formation in mice 14 days postperfusion. CatK deficiency significantly reduced lesion CD4 + T-cell content, total lesion and medial cell proliferation and apoptosis, medial smooth muscle cell (SMC) loss, elastinolytic CatL and CatS expression, and elastin fragmentation, but it did not affect AAA lesion Mac-3 + macrophage accumulation or CD31 + microvessel numbers. In vitro studies revealed that CatK contributed importantly to CD4 + T-cell proliferation, SMC apoptosis, and other cysteinyl cathepsin and matrix metalloproteinase expression and activities in SMCs and endothelial cells but played negligible roles in microvessel growth and monocyte migration. AAA lesions from CatK-deficient mice showed reduced elastinolytic cathepsin activities compared with those from wild-type control mice. Conclusion-: This study demonstrates that CatK plays an essential role in AAA formation by promoting T-cell proliferation, vascular SMC apoptosis, and elastin degradation and by affecting vascular cell protease expression and activities.

Idioma originalEnglish (US)
Páginas (desde-hasta)15-23
Número de páginas9
PublicaciónArteriosclerosis, Thrombosis, and Vascular Biology
Volumen32
N.º1
DOI
EstadoPublished - ene 2012
Publicado de forma externa

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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