title: Polychlorinated biphenyl 77 augments angiotensin II-induced atherosclerosis and abdominal aortic aneurysms in male apolipoprotein E deficient mice.
abstract: Infusion of angiotensin II (AngII) to hyperlipidemic mice augments atherosclerosis and causes formation of abdominal aortic aneurysms (AAAs). Each of these AngII-induced vascular pathologies exhibit pronounced inflammation. Previous studies demonstrated that coplanar polychlorinated biphenyls (PCBs) promote inflammation in endothelial cells and adipocytes, two cell types implicated in AngII-induced vascular pathologies. The purpose of this study was to test the hypothesis that administration of PCB77 to male apolipoprotein E (ApoE) -/- mice promotes AngII-induced atherosclerosis and AAA formation. Male ApoE-/- mice were administered vehicle or PCB77 (49 mg/kg, i.p.) during week 1 and 4 (2 divided doses/week) of AngII infusion. Body weights and total serum cholesterol concentrations were not influenced by administration of PCB77. Systolic blood pressure was increased in AngII-infused mice administered PCB77 compared to vehicle (156±6 vs 137±5 mmHg, respectively). The percentage of aortic arch covered by atherosclerotic lesions was increased in AngII-infused mice administered PCB77 compared to vehicle (2.0±0.4 vs 0.9±0.1%, respectively). Lumen diameters of abdominal aortas determined by in vivo ultrasound and external diameters of excised suprarenal aortas were increased in AngII-infused mice administered PCB77 compared to vehicle. In addition, AAA incidence increased from 47 to 85% in AngII-infused mice administered PCB77. Adipose tissue in close proximity to AAAs from mice administered PCB77 exhibited increased mRNA abundance of proinflammatory cytokines and elevated expression of components of the renin-angiotensin system (angiotensinogen, angiotensin type 1a receptor (AT1aR)). These results demonstrate that PCB77 augments AngII-induced atherosclerosis and AAA formation.
authors.affiliation: Graduate Center for Nutritional Sciences, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0200, USA.
authors.forename: Violeta
authors.initials: V
authors.lastname: Arsenescu
authors.forename: Razvan
authors.initials: R
authors.lastname: Arsenescu
authors.forename: Madhura
authors.initials: M
authors.lastname: Parulkar
authors.forename: Michael
authors.initials: M
authors.lastname: Karounos
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Nicki
authors.initials: N
authors.lastname: Baker
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cassis
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced*; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000139:chemically induced*; D001794:Blood Pressure / Q000187:drug effects; D004357:Drug Synergism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011078:Polychlorinated Biphenyls / Q000009:adverse effects*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001057:Apolipoproteins E; D000804:Angiotensin II; D011078:Polychlorinated Biphenyls; C028451:3,4,3',4'-tetrachlorobiphenyl