This Article Full Text Full Text (PDF) Alert me when this article is cited 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 Holm, P. Articles by Stender, S. Search for Related Content PubMed PubMed Citation Articles by Holm, P. Articles by Stender, S.

(Circulation. 1998;98:2731-2737.)
© 1998 American Heart Association, Inc.

Basic Science Reports

Gender Gap in Aortic Cholesterol Accumulation in Cholesterol-Clamped Rabbits

Role of the Endothelium and Mononuclear-Endothelial Cell Interaction

Pernille Holm, MD; Heidi L. Andersen, MS; Gry Arrøe, MD; Steen Stender, MD, PhD

From Novo Nordisk A/S (P.H., H.L.A.), Måløv, Denmark, and Clinical Institute, Odense University (G.A., S.S.), Odense, Denmark.

Correspondence to Pernille Holm, MD, Department of Women's Healthcare Biology, Novo Nordisk Park, 2760 Måløv, Denmark. E-mail phlm{at}novo.dk

Background—The purpose of the present study was to investigate plasma lipid–independent mechanisms for the sex difference in the development of atherosclerosis.

Methods and Results—In the first experiment, 20 male and 20 female rabbits were balloon-injured in the middle thoracic aorta and maintained at the same plasma cholesterol level of 25 mmol/L by use of individualized cholesterol feeding for 13 weeks. In the undamaged aorta, female rabbits had accumulated less than half the amount of cholesterol found in male rabbits (P<0.05). In the balloon-injured aorta, cholesterol accumulation was 3- to 4-fold higher than in the undamaged aorta, with no difference between groups. When cholesterol accumulation data for the balloon-injured aorta were separately assessed for blue (deendothelialized) and white (reendothelialized) tissue, blue tissue surprisingly revealed a reverse gender gap, ie, a significantly higher accumulation of cholesterol in females than in males (P<0.05). White tissue, which constituted the majority of the balloon-injured area, showed no difference in aortic cholesterol accumulation between groups. In the second experiment, 6 male and 6 female rabbits were fed standard rabbit pellets and 6 male and 6 female rabbits were fed a 0.5% cholesterol-enriched chow for 2 weeks. Mononuclear cell binding was 5-fold higher in aortic segments from hypercholesterolemic than from normocholesterolemic rabbits (P<0.001). In hypercholesterolemic rabbits, cell binding was significantly lower in female than in male rabbits (P<0.05) and showed higher values in atherosclerosis-prone regions. These differences were not found in normocholesterolemic animals.

Conclusions—The present results suggest that female atheroprotection is independent of sex differences in plasma cholesterol but vitally dependent on the state of the arterial endothelium and involves mononuclear-endothelial cell adhesion as an early step.

Key Words: aorta • atherosclerosis • balloon • endothelium • leukocytes

This article has been cited by other articles:

				A. K. Death, K. C. Y. McGrath, M. A. Sader, S. Nakhla, W. Jessup, D. J. Handelsman, and D. S. Celermajer Dihydrotestosterone Promotes Vascular Cell Adhesion Molecule-1 Expression in Male Human Endothelial Cells via a Nuclear Factor-{kappa}B-Dependent Pathway Endocrinology, April 1, 2004; 145(4): 1889 - 1897. [Abstract] [Full Text] [PDF]

				P. Y. Liu, A. K. Death, and D. J. Handelsman Androgens and Cardiovascular Disease Endocr. Rev., June 1, 2003; 24(3): 313 - 340. [Abstract] [Full Text] [PDF]

				G. Wang, C. W.H. Woo, F. L. Sung, Y. L. Siow, and K. O Increased Monocyte Adhesion to Aortic Endothelium in Rats With Hyperhomocysteinemia: Role of Chemokine and Adhesion Molecules Arterioscler. Thromb. Vasc. Biol., November 1, 2002; 22(11): 1777 - 1783. [Abstract] [Full Text] [PDF]

				C. S. Hayward, R. P. Kelly, and P. Collins The roles of gender, the menopause and hormone replacement on cardiovascular function Cardiovasc Res, April 1, 2000; 46(1): 28 - 49. [Full Text] [PDF]

				T. Hayashi, T. Esaki, E. Muto, H. Kano, Y. Asai, N. K. Thakur, D. Sumi, M. Jayachandran, and A. Iguchi Dehydroepiandrosterone Retards Atherosclerosis Formation Through Its Conversion to Estrogen : The Possible Role of Nitric Oxide Arterioscler. Thromb. Vasc. Biol., March 1, 2000; 20(3): 782 - 792. [Abstract] [Full Text] [PDF]

				P. Holm, H. L. Andersen, M. R. Andersen, E. Erhardtsen, and S. Stender The Direct Antiatherogenic Effect of Estrogen Is Present, Absent, or Reversed, Depending on the State of the Arterial Endothelium : A Time Course Study in Cholesterol-Clamped Rabbits Circulation, October 19, 1999; 100(16): 1727 - 1733. [Abstract] [Full Text] [PDF]