Cathepsin L expression and regulation in human abdominal aortic aneurysm, atherosclerosis, and vascular cells

Jian Liu, Galina K. Sukhova, Jin Tian Yang, Jiusong Sun, Likun Ma, An Ren, Wei Hua Xu, Huanxiang Fu, Gregory M. Dolganov, Chengcheng Hu, Peter Libby, Guo Ping Shi

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)302-311
Number of pages10
JournalAtherosclerosis
Volume184
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

Keywords

  • Abdominal aortic aneurysm
  • Atheroslcerosis
  • Cathepsin L
  • Collagenase
  • Elastase
  • Inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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