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Publication : Deficiency of the cysteine protease cathepsin S impairs microvessel growth.

First Author  Shi GP Year  2003
Journal  Circ Res Volume  92
Issue  5 Pages  493-500
PubMed ID  12600886 Mgi Jnum  J:109410
Mgi Id  MGI:3628882 Doi  10.1161/01.RES.0000060485.20318.96
Citation  Shi GP, et al. (2003) Deficiency of the cysteine protease cathepsin S impairs microvessel growth. Circ Res 92(5):493-500
abstractText  During angiogenesis, microvascular endothelial cells (ECs) secrete proteinases that permit penetration of the vascular basement membrane as well as the interstitial extracellular matrix. This study tested the hypothesis that cathepsin S (Cat S) contributes to angiogenesis. Treatment of cultured ECs with inflammatory cytokines or angiogenic factors stimulated the expression of Cat S, whereas inhibition of Cat S activity reduced microtubule formation by impairing cell invasion. ECs from Cat S-deficient mice showed reduced collagenolytic activity and impaired invasion of collagens type I and IV. Cat S-deficient mice displayed defective microvessel development during wound repair. This abnormal angiogenesis occurred despite normal vascular endothelial growth factor and basic fibroblast growth factor levels, implying an essential role for extracellular matrix degradation by Cat S during microvessel formation. These results demonstrate a novel function of endothelium-derived Cat S in angiogenesis.
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