This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 28/7/1251    most recent ATVBAHA.107.160382v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Henriques, T. Articles by Cassis, L. A. Search for Related Content PubMed PubMed Citation Articles by Henriques, T. Articles by Cassis, L. A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information Aortic Aneurysm

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1251.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Androgen Increases AT1a Receptor Expression in Abdominal Aortas to Promote Angiotensin II–Induced AAAs in Apolipoprotein E–Deficient Mice

Tracy Henriques; Xuan Zhang; Frederique B. Yiannikouris; Alan Daugherty; Lisa A. Cassis

From the Graduate Center for Toxicology (T.H., X.Z.), Cardiovascular Research Center (A.D.), and the Graduate Center for Nutritional Sciences (F.B.Y., L.A.C.), University of Kentucky, Lexington.

Correspondence to Lisa A. Cassis, PhD, Professor and Chair, 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— Castration of male apolipoprotein E–deficient (apoE^–/–) mice reduces angiotensin II (Ang II)–induced abdominal aorta aneurysms (AAAs) to that of female mice. The purpose of this study was to determine whether this reduction is attributable to androgen-mediated regulation of aortic Ang II type 1A receptors (AT1aR).

Methods and Results— AT1aR mRNA abundance in the AAA-prone region of abdominal aortas was 8-fold greater compared to thoracic aortas of male but not female mice. AT1aR mRNA abundance decreased after castration in abdominal but not thoracic aortas of male mice. Dihydrotestosterone (DHT, 0.16 mg/d) administration to castrated male mice restored AT1aR mRNA abundance in abdominal aortas but had no effect in thoracic aortas. DHT also increased AT1aR mRNA abundance in abdominal aortas from female mice. Castrated male or female apoE^–/– mice were administered DHT during infusion of saline or Ang II (1000 ng/kg/min for 28 days). DHT administration did not alter serum cholesterol concentrations, lipoprotein distributions, or atherosclerotic lesion areas in either male or female mice. However, administration of DHT increased AAA incidence in male (27% placebo versus 75% DHT) and female mice (28% placebo versus 64% DHT).

Conclusions— Androgen promotes AT1aR mRNA abundance in abdominal aortas associated with increased Ang II–induced AAAs.

Castration decreases AT1aR mRNA abundance in abdominal aortas from male and female apoE^–/– mice, whereas DHT administration increased AT1aR mRNA abundance. DHT administration increased AAA incidence in castrated males and promoted AAAs in female mice. These results demonstrate that androgen increases AT1aR abundance in abdominal aortas to promote AAA formation.

Key Words: angiotensin • aneurysms • androgen • atherosclerosis • sex hormones

This article has been cited by other articles:

				L. A. Cassis, M. Gupte, S. Thayer, X. Zhang, R. Charnigo, D. A. Howatt, D. L. Rateri, and A. Daugherty ANG II infusion promotes abdominal aortic aneurysms independent of increased blood pressure in hypercholesterolemic mice Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1660 - H1665. [Abstract] [Full Text] [PDF]

				J. T Powell and P. E Norman Abdominal aortic aneurysm events in postmenopausal women BMJ, October 14, 2008; 337(oct14_2): a1894 - a1894. [Full Text]