Metalloproteinase-9 contributes to endothelial dysfunction in atherosclerosis via protease activated receptor-1

• DOI: 10.1371/journal.pone.0171427
• Publication Date: 2017-02-06T19:02:40Z
• Authors: Jon M. Florence; Agnieszka Krupa; Laela M. Booshehri; Timothy C. Allen; Anna K. Kurdowska
• Keywords: Mice, Knockout; 0301 basic medicine; Science; Q; R; Endothelial Cells; Atherosclerosis; Immunohistochemistry; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Apolipoproteins E; 0302 clinical medicine; Matrix Metalloproteinase 9; Human Umbilical Vein Endothelial Cells; Medicine; Animals; Humans; Receptor, PAR-1; Biomarkers; Research Article; Signal Transduction

The atherosclerotic process begins when vascular endothelial cells undergo pro-inflammatory changes such as aberrant activation to dysfunctional phenotypes and apoptosis, leading loss of integrity. Our laboratory has demonstrated that exposure mice second hand smoke triggers an increase in expression metalloproteinase-9. Further, metalloproteinase-9 released by smoke—activated leukocytes may propagate pro-atherogenic alterations cells. We have shown levels were increased the plasma from apolipoprotein E deficient (ApoE-/-) exposed relative non-exposed controls. Moreover, we collected data two different, but complementary, treatments mice. Animals received either cell specific directed siRNA minimize neutrophils cells, or a pharmacological inhibitor Bruton's tyrosine kinase which indirectly limits production neutrophils. These reduced improved overall health. also could activate induce their apoptosis via cleavage protease activated receptor-1. In summary, better understanding metalloproteinase-9's pathogenic capabilities well novel signaling pathways involved lead development provide additional benefits atherosclerosis patients with history exposure.