Document Detail


Angiotensin II infusion promotes ascending aortic aneurysms: attenuation by CCR2 deficiency in apoE-/- mice.
MedLine Citation:
PMID:  20088827     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AngII (angiotensin II) induces atherosclerosis and AAAs (abdominal aortic aneurysms) through multiple proposed mechanisms, including chemotaxis. Therefore, we determined the effects of whole-body deficiency of the chemokine receptor CCR2 (CC chemokine receptor 2) on these diseases. To meet this objective, apoE (apolipoprotein E)-/- mice that were either CCR2+/+ or CCR2-/-, were infused with either saline or AngII (1000 ng.kg-1 of body weight.min-1) for 28 days via mini-osmotic pumps. Deficiency of CCR2 markedly attenuated both atherosclerosis and AAAs, unrelated to systolic blood pressure or plasma cholesterol concentrations. During the course of the present study, we also observed that AngII infusion led to large dilatations that were restricted to the ascending aortic region of apoE-/- mice. The aortic media in most of the dilated area was thickened. In regions of medial thickening, distinct elastin layers were discernable. There was an expansion of the distance between elastin layers in a gradient from the intimal to the adventitial aspect of the media. This pathology differed in a circumscribed area of the anterior region of ascending aortas in which elastin breaks were focal and almost transmural. All regions of the ascending aorta of AngII-infused mice had diffuse medial macrophage accumulation. Deficiency of CCR2 greatly attenuated the AngII-induced lumen dilatation in the ascending aorta. This new model of ascending aortic aneurysms has pathology that differs markedly from AngII-induced atherosclerosis or AAAs, but all vascular pathologies were attenuated by CCR2 deficiency.
Authors:
Alan Daugherty; Debra L Rateri; Israel F Charo; A Phillip Owens; Deborah A Howatt; Lisa A Cassis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-03-09
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  118     ISSN:  1470-8736     ISO Abbreviation:  Clin. Sci.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-03-09     Completed Date:  2010-06-29     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  681-9     Citation Subset:  IM    
Affiliation:
Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40536, U.S.A. Alan.Daugherty@uky.edu
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / pharmacology
Animals
Aorta / drug effects,  pathology
Aortic Aneurysm / chemically induced*,  metabolism,  pathology
Apolipoproteins E / deficiency,  genetics
Blood Pressure / physiology
Body Weight / physiology
Cholesterol / blood
Disease Models, Animal
Hypercholesterolemia / complications
Lipids / blood
Male
Mice
Mice, Knockout
Receptors, CCR2 / deficiency*,  physiology
Vasodilation / drug effects
Grant Support
ID/Acronym/Agency:
HL52773/HL/NHLBI NIH HHS; HL80100/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoproteins E; 0/Ccr2 protein, mouse; 0/Lipids; 0/Receptors, CCR2; 11128-99-7/Angiotensin II; 57-88-5/Cholesterol
Comments/Corrections

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