title: Serine protease inhibitor A3 in atherosclerosis and aneurysm disease.
abstract: 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.affiliation: Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden. dick.wagsater@liu.se
authors.forename: Dick
authors.initials: D
authors.lastname: Wågsäter
authors.forename: Daniel
authors.initials: D
authors.lastname: Johansson
authors.forename: Vincent
authors.initials: V
authors.lastname: Fontaine
authors.forename: Emina
authors.initials: E
authors.lastname: Vorkapic
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bäcklund
authors.forename: Anton
authors.initials: A
authors.lastname: Razuvaev
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Mäyränpää
authors.forename: Charlotta
authors.initials: C
authors.lastname: Hjerpe
authors.forename: Kenneth
authors.initials: K
authors.lastname: Caidahl
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.forename: Anders
authors.initials: A
authors.lastname: Franco-Cereceda
authors.forename: Johannes
authors.initials: J
authors.lastname: Wilbertz
authors.forename: Jesper
authors.initials: J
authors.lastname: Swedenborg
authors.forename: Xinghua
authors.initials: X
authors.lastname: Zhou
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
mesh_terms: D000783:Aneurysm / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D056649:Cathepsin G / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010196:Pancreatic Elastase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*; D000514:alpha 1-Antichymotrypsin / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D000514:alpha 1-Antichymotrypsin; D056649:Cathepsin G; D010196:Pancreatic Elastase; D002122:Calcium Chloride