Deficiency of cathepsin S reduces atherosclerosis in LDL receptor–deficient mice
Author
Zhang, Yaou
Pan, Jie-Hong
Wada, Youichiro
Yamamoto, Takashi
Naito, Makoto
Kodama, Tatsuhiko
Tsimikas, Sotirios
Witztum, Joseph L.
Lu, Michael L.
Sakara, Yasuhiko
Chin, Michael T.
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1172/JCI14915Metadata
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Sukhova, Galina K., Yaou Zhang, Jie-Hong Pan, Youichiro Wada, Takashi Yamamoto, Makoto Naito, Tatsuhiko Kodama, et al. 2003. “Deficiency of Cathepsin S Reduces Atherosclerosis in LDL Receptor–deficient Mice.” J. Clin. Invest. 111 (6) (March 15): 897–906. doi:10.1172/jci14915.Abstract
Human atherosclerotic lesions overexpress the lysosomal cysteine protease cathepsin S (Cat S), one of the most potent mammalian elastases known. In contrast, atheromata have low levels of the endogenous Cat S inhibitor cystatin C compared with normal arteries, suggesting involvement of this protease in atherogenesis. The present study tested this hypothesis directly by crossing Cat S–deficient (CatS–/–) mice with LDL receptor–deficient (LDLR–/–) mice that develop atherosclerosis on a high-cholesterol diet. Compared with LDLR–/– mice, double-knockout mice (CatS–/–LDLR–/–) developed significantly less atherosclerosis, as indicated by plaque size (plaque area and intimal thickening) and stage of development. These mice also had markedly reduced content of intimal macrophages, lipids, smooth muscle cells, collagen, CD4+ T lymphocytes, and levels of IFN-γ. CatS–/–LDLR–/– monocytes showed impaired subendothelial basement membrane transmigration, and aortas from CatS–/–LDLR–/– mice had preserved elastic laminae. These findings establish a pivotal role for Cat S in atherogenesis.Other Sources
http://www.ncbi.nlm.nih.gov/pubmed/12639996Terms of Use
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