Document Detail


Serine protease inhibitor A3 in atherosclerosis and aneurysm disease.
MedLine Citation:
PMID:  22580763     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Remodeling of extracellular matrix (ECM) plays an important role in both atherosclerosis and aneurysm disease. Serine protease inhibitor A3 (serpinA3) is an inhibitor of several proteases such as elastase, cathepsin G and chymase derived from mast cells and neutrophils. In this study, we investigated the putative role of serpinA3 in atherosclerosis and aneurysm formation. SerpinA3 was expressed in endothelial cells and medial smooth muscle cells in human atherosclerotic lesions and a 14-fold increased expression of serpinA3n mRNA was found in lesions from Apoe-/- mice compared to lesion-free vessels. In contrast, decreased mRNA expression (-80%) of serpinA3 was found in biopsies of human abdominal aortic aneurysm (AAA) compared to non-dilated aortas. Overexpression of serpinA3n in transgenic mice did not influence the development of atherosclerosis or CaCl2-induced aneurysm formation. In situ zymography analysis showed that the transgenic mice had lower cathepsin G and elastase activity, and more elastin in the aortas compared to wild-type mice, which could indicate a more stable aortic phenotype. Differential vascular expression of serpinA3 is clearly associated with human atherosclerosis and AAA but serpinA3 had no major effect on experimentally induced atherosclerosis or AAA development in mouse. However, serpinA3 may be involved in a phenotypic stabilization of the aorta.
Authors:
Dick Wågsäter; Daniel Johansson; Vincent Fontaine; Emina Vorkapic; Alexandra Bäcklund; Anton Razuvaev; Mikko I Mäyränpää; Charlotta Hjerpe; Kenneth Caidahl; Anders Hamsten; Anders Franco-Cereceda; Johannes Wilbertz; Jesper Swedenborg; Xinghua Zhou; Per Eriksson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-09
Journal Detail:
Title:  International journal of molecular medicine     Volume:  -     ISSN:  1791-244X     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
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