Geary R L, Adams M R, Benjamin M E, Williams J K
Comparative Medicine Clinical Research Center and Division of Surgical Sciences-General, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157-1040, USA.
J Am Coll Cardiol. 1998 Apr;31(5):1158-64. doi: 10.1016/s0735-1097(98)00042-4.
This study sought to determine the effects of estrogen treatment on atherosclerosis progression and the proliferative and structural responses of the atherosclerotic arteries to injury.
Estrogen treatment suppresses the intimal response to arterial injury in nonatherosclerotic rodents and rabbits and inhibits the in vitro proliferation of smooth muscle cells. However, the effect of estrogen on the response of atherosclerotic arteries to transmural injury, as occurs in balloon catheter angioplasty in humans, is unknown.
Forty-six ovariectomized cynomolgus monkeys were fed an atherogenic diet for 30 months; 25 received 175 microg/day of conjugated equine estrogens, and 21 served as untreated control animals. All animals underwent balloon catheter injury of the left iliac artery. Subsets of animals underwent a necropsy study at 4, 7, 14 and 28 days after injury; injured and contralateral (uninjured) arteries were pressure-fixed and evaluated morphometrically.
Estrogen treatment resulted in a 37% decrease (p < 0.05) in atherosclerosis (plaque area) in the uninjured artery. In response to injury, arterial cell proliferation increased at days 4 and 7, and intimal area was increased two- to threefold at day 28 (p < 0.05). Although estrogen treatment resulted in a trend toward decreased arterial cell proliferation at day 4, there was evidence of increased cell proliferation in both media and intima at day 7 (p < 0.05). However, there was no effect of estrogen treatment on intimal area or indexes of arterial remodeling in the injured artery at day 28 (p > 0.4). CONCLUSIONS. In contrast to previous studies of nonatherosclerotic animals, the results indicate that in the circumstance of transmural injury to arteries of primates with preexisting atherosclerosis, estrogen does not suppress arterial neointimal or structural responses to injury.
本研究旨在确定雌激素治疗对动脉粥样硬化进展以及动脉粥样硬化动脉对损伤的增殖和结构反应的影响。
雌激素治疗可抑制非动脉粥样硬化啮齿动物和兔子对动脉损伤的内膜反应，并抑制平滑肌细胞的体外增殖。然而，雌激素对人类球囊导管血管成形术中发生的动脉粥样硬化动脉对透壁损伤的反应的影响尚不清楚。
46只去卵巢食蟹猴接受致动脉粥样硬化饮食30个月；25只接受175微克/天的结合马雌激素，21只作为未治疗的对照动物。所有动物均接受左髂动脉球囊导管损伤。部分动物在损伤后4、7、14和28天进行尸检研究；将损伤侧和对侧（未损伤）动脉进行压力固定并进行形态学评估。
雌激素治疗使未损伤动脉的动脉粥样硬化（斑块面积）减少了37%（p<0.05）。对损伤的反应是，动脉细胞增殖在第4天和第7天增加，内膜面积在第28天增加了两到三倍（p<0.05）。尽管雌激素治疗在第4天导致动脉细胞增殖有减少的趋势，但在第7天有证据表明中膜和内膜的细胞增殖均增加（p<0.05）。然而，雌激素治疗对第28天损伤动脉的内膜面积或动脉重塑指数没有影响（p>0.4）。结论。与先前对非动脉粥样硬化动物的研究相反，结果表明，在已有动脉粥样硬化的灵长类动物动脉发生透壁损伤的情况下，雌激素不会抑制动脉内膜或对损伤的结构反应。
