Gender gap in aortic cholesterol accumulation in cholesterol-clamped rabbits - Role of the endothelium and mononuclear-endothelial cell interaction

Background-The purpose of the present study was to investigate plasma lipid -independent mechanisms for the sex difference in the development of athero sclerosis. 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 sam e plasma cholesterol level of approximate to 25 mmol/L by use of individual ized cholesterol feeding for 13 weeks. In the undamaged aorta, female rabbi ts had accumulated less than half the amount of cholesterol found in male r abbits (P<0.05). In the balloon-injured aorta, cholesterol accumulation was 3- to 4-fold higher than in the undamaged aorta, with no difference betwee n groups. When cholesterol accumulation data for the balloon-injured aorta were separately assessed for blue (deendothelialized) and white (reendothel ialized) tissue, blue tissue surprisingly revealed a reverse gender gap, ie , a significantly higher accumulation of cholesterol in females than in mal es (P<0.05). White tissue, which constituted the majority of the balloon-in jured area, showed no difference in aortic cholesterol accumulation between groups. In the second experiment, 6 male and 6 female rabbits were fed sta ndard rabbit pellets and 6 male and 6 female rabbits were fed a 0.5% choles terol-enriched chow for 2 weeks. Mononuclear cell binding was 5-fold higher in aortic segments from hypercholesterolemic than from normocholesterolemi c rabbits (P<0.001). In hypercholesterolemic rabbits, cell binding was sign ificantly lower in female than in male rabbits (P<0.05) and showed higher v alues in atherosclerosis-prone regions. These differences were not found in normocholesterolemic animals. Conclusions-The present results suggest that female atheroprotection is ind ependent 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.