Cathepsin L expression and regulation in human abdominal aortic aneurysm, atherosclerosis, and vascular cells
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Dolganov, Gregory M.
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CitationLiu, Jian, Galina K. Sukhova, Jin-Tian Yang, Jiusong Sun, Likun Ma, An Ren, Wei-Hua Xu, et al. 2006. “Cathepsin L Expression and Regulation in Human Abdominal Aortic Aneurysm, Atherosclerosis, and Vascular Cells.” Atherosclerosis 184 (2) (February): 302–311. doi:10.1016/j.atherosclerosis.2005.05.012.
AbstractThe cysteine protease cathepsin L is one of the most potent mammalian elastases and collagenases, widely expressed at basal levels in most tested tissues and cell types, and regulated by pro-inflammatory stimuli. The inflammatory arterial diseases abdominal aortic aneurysm (AAA) and atherosclerosis involve extensive vascular remodeling that requires elastolysis and collagenolysis. This study examined the hypothesis that cathepsin L is over-expressed in human AAA and atherosclerotic lesions and its expression in vascular cell types found in these lesions is regulated by pro-inflammatory cytokines. Immunohistochemical and tissue extract immunoblot analysis demonstrated increased expression of cathepsin L in human AAA and atheromata and localized its expression to lesional smooth muscle cells (SMC), endothelial cells (EC), and macrophages. In primary cultured human SMC, EC, and monocyte-derived macrophages, pro-inflammatory cytokines or growth factors induced the expression of cathepsin L and its activity against extracellular collagen and elastin. Patients with coronary artery stenosis (n = 65) had higher serum cathepsin L levels than those without lesions detectable by quantitative coronary angiography (n = 30) (1.47 ± 0.33 ng/ml versus 0.60 ± 0.06 ng/ml, p < 0.02). A strong correlation between the percent of stenosis of left anterior descending coronary artery and serum cathepsin L levels in patients with stenosis (R = 0.542, p < 0.0001), also suggests involvement of cathepsin L in these vascular diseases.
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