Adams M R, Williams J K, Kaplan J R
Department of Comparative Medicine, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1040, USA.
Arterioscler Thromb Vasc Biol. 1995 May;15(5):562-70. doi: 10.1161/01.atv.15.5.562.
The factors responsible for the marked gender differences in risk of coronary heart disease and atherosclerosis severity remain largely undetermined. While some clinical and experimental evidence supports a protective effect of endogenous estrogen on the initiation and progression of atherosclerosis and incidence of coronary heart disease, much of the epidemiological data do not support this conclusion. The possibility that endogenous androgens may have adverse effects on atherosclerosis progression and coronary risk has received little attention. We investigated the effects of experimentally induced hyperandrogenism in female cynomolgus monkeys with diet-induced atherosclerosis. Animals were assigned randomly to one of four treatment groups: (1) untreated controls, (2) ovariectomized (sex hormone-deficient) controls, (3) treated with androstenedione and estrone (mild hyperandrogenism), or (4) treated with testosterone (male plasma androgen pattern). At necropsy, coronary atherosclerosis was approximately twice as extensive (P < .05) in testosterone-treated animals relative to untreated controls, while treatment with androstenedione and estrone had no effect on atherosclerosis extent. Coronary plaque size was positively correlated with lumen size in intact and ovariectomized controls; however, there was no evidence of a similar relation between animals in either androgen treatment group. The atherogenic effects of testosterone were independent of variations in plasma lipoprotein and nonlipoprotein risk variables. Although chronic hyperandrogenism had adverse effects on atherosclerosis progression, it reversed (P < .03) atherosclerosis-related impairment of endothelium-dependent vasodilator responses. We conclude that an experimentally induced male plasma androgen pattern results in exacerbation of diet-induced atherosclerosis-related arterial remodeling in female monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)
冠心病风险及动脉粥样硬化严重程度存在显著性别差异的相关因素，在很大程度上仍未明确。虽然一些临床和实验证据支持内源性雌激素对动脉粥样硬化的发生发展及冠心病发病率具有保护作用，但许多流行病学数据并不支持这一结论。内源性雄激素可能对动脉粥样硬化进展及冠心病风险产生不利影响这一可能性，几乎未受到关注。我们研究了实验性诱导的高雄激素血症对饮食诱导的动脉粥样硬化雌性食蟹猴的影响。将动物随机分为四个治疗组之一：（1）未治疗的对照组，（2）卵巢切除（性激素缺乏）对照组，（3）用雄烯二酮和雌酮治疗（轻度高雄激素血症），或（4）用睾酮治疗（男性血浆雄激素模式）。尸检时，与未治疗的对照组相比，用睾酮治疗的动物冠状动脉粥样硬化程度约为其两倍（P < 0.05），而用雄烯二酮和雌酮治疗对粥样硬化程度无影响。在完整和卵巢切除的对照组中，冠状动脉斑块大小与管腔大小呈正相关；然而，在任何一个雄激素治疗组的动物中均未发现类似关系的证据。睾酮的致动脉粥样硬化作用与血浆脂蛋白和非脂蛋白风险变量的变化无关。虽然慢性高雄激素血症对动脉粥样硬化进展有不利影响，但它逆转了（P < 0.03）与动脉粥样硬化相关的内皮依赖性血管舒张反应受损。我们得出结论，实验性诱导的男性血浆雄激素模式会导致雌性猴子饮食诱导的动脉粥样硬化相关动脉重塑加剧。（摘要截短至250字）
