%0 Journal Article
%T Characterization of death receptor 3©\dependent aortic changes during inflammatory arthritis
%A Anwen S. Williams
%A Derek Lang
%A Eddie C. Y. Wang
%A Jessica O. Williams
%J Archive of "Pharmacology Research & Perspectives".
%D 2016
%R 10.1002/prp2.240
%X Murine collagen©\induced arthritis (mCIA) is characterized by decreased vascular constriction responses and increased MMP©\9. Here, we describe additional histological alterations within the aorta and surrounding perivascular adipose tissue (PVAT), study the role of PVAT in constriction response, and investigate the potential involvement of death receptor 3 (DR3). mCIA was induced in wild©\type (WT) and DR3£¿/£¿ mice with nonimmunized, age©\matched controls. Vascular function was determined in isolated aortic rings ¡ÀPVAT, using isometric tension myography, in response to cumulative serotonin concentrations. Cellular expression of F4/80 (macrophages), Ly6G (neutrophils), DR3, and MMP©\9 was determined using immunohistochemistry. In WTs, arthritis©\induced vascular dysfunction was associated with increased F4/80+ macrophages and increased DR3 expression in the aorta and PVAT. MMP©\9 was also up©\regulated in PVAT, but did not correlate with alterations of PVAT intact constriction. DR3£¿/£¿ mice inherently showed increased leukocyte numbers and MMP©\9 expression in the PVAT, but retained the same nonarthritic constriction response as DR3WT mice ¡ÀPVAT. Arthritic DR3£¿/£¿ mice had a worsened constriction response than DR3WT and showed an influx of neutrophils to the aorta and PVAT. Macrophage numbers were also up©\regulated in DR3£¿/£¿ PVAT. Despite this influx, PVAT intact DR3£¿/£¿ constriction responses were restored to the same level as DR3WT. Impaired vascular constriction in inflammatory arthritis occurs independently of total MMP©\9 levels, but correlates with macrophage and neutrophil ingress. Ablating DR3 worsens the associated vasculature dysfunction, however, DR3£¿/£¿ PVAT is able to protect the aorta against aberrant vasoconstriction caused in this model
%K Death receptor 3
%K inflammatory arthritis
%K inflammatory ingress
%K vascular constriction
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915515/