EFFECTS OF ANDROGENS ON CORONARY-ARTERY ATHEROSCLEROSIS AND ATHEROSCLEROSIS-RELATED IMPAIRMENT OF VASCULAR RESPONSIVENESS
EFFECTS OF ANDROGENS ON CORONARY-ARTERY ATHEROSCLEROSIS AND ATHEROSCLEROSIS-RELATED IMPAIRMENT OF VASCULAR RESPONSIVENESS
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DOI：
10.1161/01.atv.15.5.562
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发表时间：
1995-05-01
影响因子：
8.7
通讯作者：
KAPLAN, JR
中科院分区：
文献类型：
--
作者：
ADAMS, MR;WILLIAMS, JK;KAPLAN, JR
导致冠心病风险和动脉粥样硬化严重程度显著性别差异的因素在很大程度上仍未确定。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和发展以及冠心病的发病率具有保护作用，但大部分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和冠状动脉风险产生不良影响的可能性很少受到关注。我们研究了雌性食蟹猴饮食诱导动脉粥样硬化实验诱导高雄激素血症的影响。将动物随机分配至四个处理组之一：（1）未处理对照组，（2）卵巢切除（性功能缺陷）对照组，（3）雄烯二酮和雌酮处理组（轻度高雄激素血症），或（4）睾酮处理组（雄性血浆雄激素模式）。尸检时，睾酮治疗组动物的冠状动脉粥样硬化程度大约是未治疗对照组的两倍（P <0.05），而雄烯二酮和雌酮治疗对动脉粥样硬化程度没有影响。在完整和卵巢切除对照组中，冠状动脉斑块大小与管腔大小呈正相关;然而，没有证据表明雄激素治疗组中的动物之间存在类似关系。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。尽管慢性高雄激素血症对动脉粥样硬化进展有不良影响，但它逆转了（P <0.03）动脉粥样硬化相关的内皮依赖性血管舒张反应的损害。我们的结论是，实验诱导的雄性血浆雄激素模式的结果加剧饮食诱导的动脉粥样硬化和动脉粥样硬化相关的动脉重塑在雌性猴子有潜在的不利影响。结果表明，睾酮可能在大多数西方社会中，相对于女性，男性动脉粥样硬化进展率增加和冠心病风险增加中起直接作用。
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 and has potentially adverse effects on atherosclerosis-related arterial remodeling in female monkeys. The results indicate that testosterone may have a direct role in the increased rate of atherosclerosis progression and increased risk of coronary heart disease seen in men, relative to women, in most Western societies.