Serine protease inhibitor A3 in atherosclerosis and aneurysm disease

Wågsäter,Dick; Johansson,Daniel; Fontaine,Vincent; Vorkapic,Emina; Bäcklund,Alexandra; Razuvaev,Anton; Mäyränpää
,Mikko  I.; Hjerpe,Charlotta; Caidahl,Kenneth; Hamsten,Anders; Franco-Cereceda,Anders; Wilbertz,Johannes; Swedenborg,Jesper; Zhou,Xinghua; Eriksson,Per

doi:10.3892/ijmm.2012.994

August 2012 Volume 30 Issue 2

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August 2012 Volume 30 Issue 2

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Article

Serine protease inhibitor A3 in atherosclerosis and aneurysm disease

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
View Affiliations / Copyright

Affiliations: Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden, Vascular Surgery Section, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden, Wihuri Research Institute, Helsinki, Finland, Clinical Physiology Unit, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden, Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden, The Karolinska Center for Transgene Technologies, Stockholm, Sweden
Pages: 288-294
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Published online on: May 9, 2012

https://doi.org/10.3892/ijmm.2012.994
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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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Serine protease inhibitor A3 in atherosclerosis and aneurysm disease

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Abstract

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