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Cathepsin L is significantly associated with apoptosis and plaque destabilization in human atherosclerosis
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
Linköping University, Department of Medical and Health Sciences, Vascular surgery. Linköping University, Faculty of Health Sciences.
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2009 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 202, no 1, 92-102 p.Article in journal (Refereed) Published
Abstract [en]

Objective: Human atherosclerotic lesions overexpress elastolytic and collagenolytic cathepsins with unclear pathological implications. The aim of this study was to investigate the relationship among expression of cathepsin L. macrophage apoptosis in coronary artery disease (CAD) patients, clinical symptoms and plaque severity Of human carotid atheroma.

Methods and results: Quantitative immunohistochemical analysis of human carotid atherosclerotic lesions (n = 49) showed that expression of lysosomal cathepsin L was significantly increased in atherosclerotic plaques with formation of the necrotic core and rupture of the cap. In those Plaques, cathepsin L was associated mainly with CD68-positive macrophages, whereas significant lower levels of smooth muscle cell actin were detected. The expression of cathepsin L in these plaques was also correlated with apoptosis and the stress protein ferritin. Plaques from symptomatic patients showed greater increased levels of cathepsin L than those front asymptomatic patients. Human monocyte-derived macrophages from CAD patients (n = 7) showed significantly higher levels of cathepsin L, cellular lipids and apoptosis versus cells from matched healthy donors (n = 7). 7Beta-hydroxycholesterol significantly enhanced cathepsin L in cells from healthy donors but not in Cells from CAD patients. Moreover. macrophage apoptosis was significantly correlated with expression of cathepsin L in cell nuclei and membranes.

Conclusion: The results Suggest that cathepsin L is involved in death of macrophages necrotic Core formation and development of atherosclerotic plaque instability. Macrophage lysosomal cathepsin L and related apoptosis may be potential targets for modulation or imaging of vulnerable plaques in human atherosclerosis.

Place, publisher, year, edition, pages
2009. Vol. 202, no 1, 92-102 p.
Keyword [en]
Atherosclerosis, Apoptosis, Cathepsin L, Lipid, Macrophage, Oxysterol
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-16750DOI: 10.1016/j.atherosclerosis.2008.03.027OAI: oai:DiVA.org:liu-16750DiVA: diva2:160525
Available from: 2009-02-14 Created: 2009-02-13 Last updated: 2014-01-17Bibliographically approved

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Li, WeiJonasson, LenaYuan, Ximing

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