Document Type
Article
Publication Date
Spring 2-6-2017
Abstract
The atherosclerotic process begins when vascular endothelial cells undergo pro-inflammatory changes such as aberrant activation to dysfunctional phenotypes and apoptosis, leading to loss of vascular integrity. Our laboratory has demonstrated that exposure of mice to second hand smoke triggers an increase in expression of metalloproteinase-9. Further, metalloproteinase-9 released by second hand smoke--activated leukocytes may propagate pro-atherogenic alterations in endothelial cells. We have shown that levels of metalloproteinase-9 were increased in the plasma from apolipoprotein E deficient (ApoE-/-) mice exposed to second hand smoke relative to non-exposed controls. Moreover, we have collected data from two different, but complementary, treatments of second hand smoke exposed atherosclerotic mice. Animals received either cell specific metalloproteinase-9 directed siRNA to minimize metalloproteinase-9 expression in neutrophils and endothelial cells, or a pharmacological inhibitor of Bruton's tyrosine kinase which indirectly limits metalloproteinase-9 production in neutrophils. These treatments reduced atherosclerotic changes in mice and improved overall vascular health. We also demonstrated that metalloproteinase-9 could activate endothelial cells and induce their apoptosis via cleavage of protease activated receptor-1. In summary, better understanding of metalloproteinase-9's pathogenic capabilities as well as novel signaling pathways involved may lead to development of treatments which may provide additional benefits to atherosclerosis patients with a history of second hand smoke exposure.
Persistent Identifier
http://hdl.handle.net/10950/4386
Publisher
PLOS One
Permanent Email Address
akurdowska@uttyler.edu
Recommended Citation
Florence, Jon M.; Krupa, Agnieszka; Booshehri, Laela M.; Allen, Timothy C.; and Kurdowska, Anna K., "Metalloproteinase-9 contributes to endothelial dysfunction in atherosclerosis via protease activated receptor-1" (2017). Cellular and Molecular Biology Faculty Publications and Presentations. Paper 7.
Description
© 2017 Florence et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.