Serine protease inhibitor A3 in atherosclerosis and aneurysm disease

International Journal of Molecular Medicine
Dick WågsäterPer Eriksson

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 effe...Continue Reading

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Citations

May 21, 2015·International Journal of Molecular Sciences·Albert M Kroon, Jan-Willem Taanman
Aug 6, 2014·Biochimica Et Biophysica Acta·Jing WangGuo-Ping Shi
Feb 4, 2014·Proteomics. Clinical Applications·Cindy SalvisbergNatacha Turck
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Jul 6, 2021·JACC. Basic to Translational Science·Yuka Shiheido-WatanabeTetsuo Sasano

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