Holm P, Andersen H L, Arrøe G, Stender S
Department of Women's HealthCare Biology, Novo Nordisk A/S, Måløv, Denmark.
Circulation. 1998 Dec 15;98(24):2731-7. doi: 10.1161/01.cir.98.24.2731.
The purpose of the present study was to investigate plasma lipid-independent mechanisms for the sex difference in the development of atherosclerosis.
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 approximately 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.
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.
本研究的目的是探讨动脉粥样硬化发展过程中性别差异的血浆脂质非依赖机制。
在第一个实验中，对20只雄性和20只雌性兔子的胸主动脉中部进行球囊损伤，并通过个体化胆固醇喂养维持血浆胆固醇水平在约25 mmol/L，持续13周。在未损伤的主动脉中，雌性兔子积累的胆固醇量不到雄性兔子的一半（P<0.05）。在球囊损伤的主动脉中，胆固醇积累比未损伤的主动脉高3至4倍，两组之间无差异。当分别评估球囊损伤主动脉的蓝色（去内皮化）和白色（再内皮化）组织的胆固醇积累数据时，蓝色组织令人惊讶地显示出性别差异反转，即雌性兔子的胆固醇积累明显高于雄性兔子（P<0.05）。构成球囊损伤区域大部分的白色组织，两组之间主动脉胆固醇积累无差异。在第二个实验中，6只雄性和6只雌性兔子喂食标准兔粮，6只雄性和6只雌性兔子喂食0.5%胆固醇丰富的饲料，持续2周。高胆固醇血症兔子主动脉段的单核细胞结合率比正常胆固醇血症兔子高5倍（P<0.001）。在高胆固醇血症兔子中，雌性兔子的细胞结合率明显低于雄性兔子（P<0.05），且在易发生动脉粥样硬化的区域显示出更高的值。在正常胆固醇血症动物中未发现这些差异。
目前的结果表明，雌性动物的动脉粥样硬化保护作用独立于血浆胆固醇的性别差异，但至关重要地依赖于动脉内皮的状态，并且涉及单核细胞与内皮细胞的粘附作为早期步骤。
