This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 29/10/1458    most recent ATVBAHA.109.192658v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Police, S. B. Articles by Cassis, L. A. PubMed PubMed Citation Articles by Police, S. B. Articles by Cassis, L. A.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1458.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Obesity Promotes Inflammation in Periaortic Adipose Tissue and Angiotensin II-Induced Abdominal Aortic Aneurysm Formation

Sara B. Police; Sean E. Thatcher; Richard Charnigo; Alan Daugherty; Lisa A. Cassis

From the Graduate Center for Nutritional Sciences (S.B.P., S.E.T., A.D., L.A.C.), the Department of Statistics (R.C.), and the Cardiovascular Research Center, Gill Heart Institute (A.D., L.A.C.), University of Kentucky, Lexington.

Correspondence to Lisa A. Cassis, PhD, Professor and Director, Graduate Center for Nutritional Sciences, Room 521b, Wethington Building, 900 S Limestone, University of Kentucky, Lexington, KY 40536-0200. E-mail lcassis{at}uky.edu

Objective— Obesity promotes macrophage infiltration into adipose tissue and is associated with increases in several cardiovascular diseases. Infusion of angiotensin II (AngII) to mice induces formation of abdominal aortic aneurysms (AAAs) with profound medial and adventitial macrophage infiltration. We sought to determine whether obesity promotes macrophage infiltration and proinflammatory cytokines in periaortic adipose tissue surrounding abdominal aortas and increases AngII-induced AAAs.

Methods and Results— Hypertrophied white adipocytes surrounded abdominal aortas, whereas brown adipocytes surrounded thoracic aortas of obese mice. mRNA abundance of macrophage proinflammatory chemokines and their receptors were elevated with obesity to a greater extent in abdominal compared to thoracic periaortic adipose tissue. Periaortic adipose tissue explants surrounding abdominal aortas of obese mice released greater concentrations of MCP-1 and promoted more macrophage migration than explants from thoracic aortas. Male C57BL/6 mice were fed a high-fat (HF) diet for 1, 2, or 4 months and then infused with AngII (1000 ng/kg/min) for 28 days. AAA incidence increased progressively with the duration of HF feeding (18%, 36%,and 60%, respectively). Similarly, AngII-infused ob/ob mice exhibited increased AAAs compared to lean controls (76% compared to 32%, respectively, P<0.05). Infusion of AngII to obese mice promoted further macrophage infiltration into periaortic and visceral adipose tissue, and obese mice exhibiting AAAs had greater macrophage content in visceral adipose tissue than mice not developing AAAs.

Conclusions— Increased macrophage accumulation in periaortic adipose tissue surrounding abdominal aortas of AngII-infused obese mice is associated with enhanced AAA formation.

Obesity increased macrophage accumulation and cytokine expression in periaortic adipose tissue surrounding abdominal aortas. Periaortic adipose explants from abdominal aortas of obese mice released MCP-1 and promoted macrophage migration more than lean mice. Obesity promoted AAA formation. Obesity increases macrophage infiltration to periaortic adipose tissue and promotes AngII-induced AAAs.

Key Words: obesity • angiotensin II • abdominal aortic aneurysm