Clarkson Thomas B, Mehaffey Margaret H
Wake Forest University Primate Center, Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1040, USA.
Am J Primatol. 2009 Sep;71(9):785-93. doi: 10.1002/ajp.20693.
The cynomolgus monkey model has contributed to significant advances regarding the understanding of coronary artery atherosclerosis of females. There are currently 8 million women in the United States living with heart disease, necessitating further study and understanding of this leading cause of morbidity and mortality for postmenopausal women. Specifically, studies involving the monkey model have allowed greater understanding of the effect of the stage of reproductive life, time since menopause, and the extent of subclinical atherosclerosis as determinates of estrogen-mediated effects on arteries. Utilizing the commonalities among monkeys and human beings, these studies have shown that postmenopausal atherosclerosis is associated with the premenopausal reproductive timeframe. In addition, monkey studies have shown that estrogen deficiency during the premenopausal stage is extremely relevant regarding the progression of atherosclerosis. After several postmenopausal years, however, studies have shown that estrogen has no beneficial effects on atherosclerosis progression and may, in fact, be deleterious. Studies using the monkey model are currently underway to investigate further uses and possibilities of postmenopausal hormone therapy for treating menopausal symptoms while protecting the breast and uterus and inhibiting the progression of coronary artery atherosclerosis. These studies will hopefully clarify the role of estrogen and eliminate the need for the possibly harmful progestin effects through the use of a highly selective estrogen receptor modulator.
食蟹猴模型在女性冠状动脉粥样硬化的理解方面取得了重大进展。目前在美国有800万女性患有心脏病,因此有必要进一步研究和了解这一绝经后女性发病和死亡的主要原因。具体而言,涉及猴模型的研究使人们能够更深入地了解生殖生命阶段、绝经后的时间以及亚临床动脉粥样硬化程度作为雌激素对动脉介导作用的决定因素所产生的影响。利用猴子和人类之间的共性,这些研究表明绝经后动脉粥样硬化与绝经前的生殖时间框架有关。此外,猴子研究表明绝经前阶段的雌激素缺乏与动脉粥样硬化的进展极为相关。然而,在绝经后的几年里,研究表明雌激素对动脉粥样硬化的进展没有有益作用,实际上可能是有害的。目前正在进行使用猴模型的研究,以进一步探索绝经后激素疗法在治疗更年期症状的同时保护乳房和子宫并抑制冠状动脉粥样硬化进展方面的其他用途和可能性。这些研究有望阐明雌激素的作用,并通过使用高度选择性雌激素受体调节剂消除可能有害的孕激素作用。