Compromised microcirculation in women with Polycystic Ovary Syndrome

多囊卵巢综合症女性的微循环受损

• 批准号: 7742059
• 负责人: NINA STACHENFELD
• 金额: $ 25.62万
• 依托单位: JOHN B. PIERCE LABORATORY, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7742059
• 关键词: Address; Affect; Age; Androgens; Blood Circulation; Blood Pressure; Blood flow; Cardiovascular Diseases; Cardiovascular system; Consensus; Cutaneous; Defect; Disease; Dose; Endothelin; Endothelin B Receptor; Endothelin-1; Estrogens; Functional disorder; Health; Heating; Histamine H1 Receptors; Hyperandrogenism; Hypertension; Insulin Resistance; Laser-Doppler Flowmetry; Lead; Left; Mediating; Microcirculation; Microdialysis; Modeling; Nerve; Nitric Oxide; Obesity; Peripheral; Peripheral Resistance; Physiological; Plasma; Polycystic Ovary Syndrome; Prostaglandins; Public Health; Research; Risk; Risk Factors; Role; Series; Skin; Sympathetic Nervous System; Testing; Testosterone; Vascular System; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Woman; cardiovascular disorder risk; cardiovascular risk factor; glucose disposal; improved; insight; men; peripheral blood; public health relevance; receptor; reproductive; research study; response; vasoconstriction

DESCRIPTION (provided by applicant): Polycystic ovary syndrome (PCOS) is the most common reproductive endocrinopathy in young women, affecting 6-10 % of women of reproductive age. Obesity, insulin resistance, hyperandrogenism and hyperestrogenism are core functional disorders of PCOS and place women at increased risk for microvascular dysfunction. Women with PCOS have greater circulating concentrations of endothelin-1 (ET-1), a potent vasoconstrictor in the microcirculation (including that of the skin), which can increase blood pressure and lead to endothelial damage. The central hypothesis of this proposal is that testosterone effects on ET-1 mediate the peripheral microvascular dysfunction associated with PCOS. This hypothesis will be tested using a prolonged skin heating model to study peripheral microvascular responsiveness. Local skin heating has been used extensively to study mechanisms controlling peripheral microcirculation under a number of physiological conditions, including obesity, insulin resistance and hypertension. The impact of testosterone or ET-1 on microvascular responsiveness to local heating has not been studied in women with or without PCOS. This proposal seeks to provide this missing information via pursuit of two Specific Aims. Specific Aim 1 will apply dose-response curves to examine the mechanism by which ET-1 influences peripheral vasodilation. Specific Aim 2 will determine the mechanism by which testosterone affects peripheral microcirculatory responsiveness in women with and without PCOS. These studies will have broad public health implications because our findings on the effect of hyperandrogenism on endothelial function may provide insights applicable to cardiovascular health in women and men. PUBLIC HEALTH RELEVANCE: Women with Polycystic Ovary Syndrome (PCOS) have greater risk for cardiovascular disease, in particular dysfunction of the peripheral circulation that can lead to hypertension and comprised glucose disposal. This research will determine the role of hyperandrogenism in microvascular responsiveness in women with PCOS, and the mechanisms by which testosterone may impact endothelial function. These studies also have broad public health implications because our findings on the effect of hyperandrogenism on endothelial function may provide insights that can improve cardiovascular health of all obese women and men.

描述（由申请人提供）：多囊卵巢综合征（PCOS）是年轻女性中最常见的生殖内分泌病，影响了6-10％的生殖年龄。肥胖，胰岛素抵抗，超雄激素和高雌激素是PCOS的核心功能障碍，使女性面临微血管功能障碍的风险增加。患有PCOS的女性具有较高的循环浓度内皮素-1（ET-1），这是微循环中有效的血管收缩剂（包括皮肤的血管收缩剂），可以增加血压并导致内皮损伤。该提议的中心假设是睾丸激素对ET-1的作用介导了与PCOS相关的周围微血管功能障碍。该假设将使用延长的皮肤加热模型进行检验，以研究周围的微血管反应性。在许多生理条件下，包括肥胖，胰岛素抵抗和高血压在内的多种生理条件下，局部皮肤加热已广泛用于研究控制周围微循环的机制。在患有或没有PCOS的女性中尚未研究睾丸激素或ET-1对局部加热微血管反应的影响。该建议旨在通过追求两个具体目标来提供此缺失的信息。具体目标1将应用剂量反应曲线来检查ET-1影响周围血管舒张的机制。具体目标2将确定睾丸激素影响有或没有PCOS的女性的外周微循环反应的机制。这些研究将具有广泛的公共卫生影响，因为我们对高狂力主义对内皮功能的影响的发现可能会提供适用于男女心血管健康的见解。公共卫生相关性：患有多囊卵巢综合征（PCOS）的女性患心血管疾病的风险更大，特别是外周循环功能障碍，可导致高血压并构成葡萄糖处置。这项研究将确定高狂力主义在PCOS女性微血管反应性中的作用，以及睾丸激素可能影响内皮功能的机制。这些研究也具有广泛的公共卫生影响，因为我们对高雄激素对内皮功能的影响的发现可能会提供见解，从而可以改善所有肥胖男女的心血管健康。