Cathepsin L expression and regulation in human abdominal aortic aneurysm, atherosclerosis, and vascular cells.
The 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.
Department of Cell and Molecular Biology, University of Science and Technology of China, Hefei, China.
Jian
J
Liu
Galina K
GK
Sukhova
Jin-Tian
JT
Yang
Jiusong
J
Sun
Likun
L
Ma
An
A
Ren
Wei-Hua
WH
Xu
Huanxiang
H
Fu
Gregory M
GM
Dolganov
Chengcheng
C
Hu
Peter
P
Libby
Guo-Ping
GP
Shi
D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D056668:Cathepsin L; D002403:Cathepsins / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000235:genetics*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D012501:Saphenous Vein / Q000378:metabolism / Q000473:pathology
D004792:Enzyme Precursors; D012333:RNA, Messenger; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse