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

Atherosclerosis. 2006 Feb;184(2):302-11. doi: 10.1016/j.atherosclerosis.2005.05.012. Epub 2005 Jun 27.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aortic Aneurysm, Abdominal / metabolism*
  • Aortic Aneurysm, Abdominal / pathology
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Cathepsin L
  • Cathepsins / biosynthesis
  • Cathepsins / genetics*
  • Cells, Cultured
  • Cysteine Endopeptidases / biosynthesis
  • Cysteine Endopeptidases / genetics*
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Enzyme Precursors / biosynthesis
  • Enzyme Precursors / genetics*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation*
  • Humans
  • In Vitro Techniques
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics*
  • Saphenous Vein / metabolism
  • Saphenous Vein / pathology


  • Enzyme Precursors
  • RNA, Messenger
  • Cathepsins
  • Cysteine Endopeptidases
  • CTSL protein, human
  • Cathepsin L
  • Ctsl protein, mouse