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Cathepsin G deficiency decreases complexity of atherosclerotic lesions in apolipoprotein E-deficient mice.
MedLine Citation:
PMID:  23934850     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cathepsin G is a serine protease with a broad range of catalytic activities including production of angiotensin II, degradation of extracellular matrix and cell-cell junctions, modulation of chemotactic responses and induction of apoptosis. Cathepsin G mRNA expression is increased in human coronary atheroma versus the normal vessel. To assess whether cathepsin G modulates atherosclerosis, cathepsin G knockout (Cstg-/-) mice were bred with apolipoprotein E knockout (Apoe-/-) mice to obtain Ctsg+/-Apoe-/- and Ctsg+/+Apoe-/- mice. Heterozygous cathepsin G deficiency led to a 70 % decrease in cathepsin G activity in bone marrow cells but this reduced activity did not impair generation of angiotensin II in bone marrow-derived macrophages (BMDM). Atherosclerotic lesions were compared in male Cstg+/-Apoe-/- and Cstg+/+Apoe-/- mice after 8 weeks on a high fat diet. Plasma cholesterol levels and cholesterol distribution within serum lipoprotein fractions did not differ between genotypes nor did the atherosclerotic lesion areas in either the aortic root or aortic arch. Cstg+/-Apoe-/- mice, however, showed a lower percentage of complex lesions within the aortic root, and a smaller number of apoptotic cells compared to Cstg+/+Apoe-/- littermates. Further, apoptotic Cstg-/- BMDM were more efficiently engulfed by phagocytic BMDM than were apoptotic Ctsg+/+ BMDM. Thus, cathepsin G activity may impair efferocytosis which could lead to an accumulation of lesion-associated apoptotic cells and the accelerated progression of early atherosclerotic lesions to more complex lesions in Apoe-/- mice.
Authors:
Naimeh Rafatian; Denuja Karunakaran; Katey J Rayner; Frans H H Leenen; Ross W Milne; Stewart C Whitman
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-8-9
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  -     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-8-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1University of Ottawa Heart Institute.
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