HORMONE THERAPY AND INFLAMMATORY CELL ADHESION MOLECULES

激素疗法和炎症细胞粘附分子

• 批准号: 6109271
• 负责人: R O CANNON
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6109271
• 关键词: antioxidants; biomarker; blood chemistry; cell adhesion molecules; clinical research; coronary disorder; estradiol; female; high risk behavior /lifestyle; hormone therapy; human subject; human therapy evaluation; inflammation; low density lipoprotein; medroxyprogesterone; postmenopause; selectins; transdermal drug delivery; vascular endothelium

Atherosclerosis is likely a chronic inflammatory disease associated with oxidation of lipoproteins. In order to investigate the effect of an estrogen with antioxidant potential on soluble markers of chronic vascular inflammation, we administered 17beta-estradiol to postmenopausal women, with measurement of cell adhesion molecules that tether and incorporate circulating inflammatory cells into the vessel wall. Twenty women were randomized to begin one-month treatment with either transdermal 17beta-estradiol 0.1 mg daily (9 women) or 17beta-estradiol 0.1 mg and medroxy-progesterone acetate 2.5 mg daily (11 women). We measured soluble E-selectin, intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) concentrations in serum, and the oxidizability of low density lipoprotein isolated from plasma (spectrophotometric diene formation assay) at baseline and following one month of treatment, with blinded performance of all assays. Hormone therapy significantly prolonged the time to onset of low density lipoprotein oxidation compared with pretreatment values (77+/-13 to 88+/-16 min, p=.003) and marginally reduced the maximum rate of oxidation (p=.077). Hormone therapy significantly lowered ICAM-1 levels by 8% (p=.009) and tended to lower E-selectin levels by 6% (p=.096) and VCAM-1 levels by 6% (p=.084). Co-administration of medroxyprogesterone acetate did not show any significant differences in the relative changes in E-selectin, ICAM-1 and VCAM-1 levels, compared to 17beta-estradiol alone (all p<.10). We conclude that hormone therapy has a favorable effect on markers of vascular inflammation, changes that may reduce the coronary artery disease risk of postmenopausal women.

动脉粥样硬化可能是一种慢性炎症 与脂蛋白氧化有关的疾病。为了 研究一种具有抗氧化潜力的雌激素对血管紧张素转换酶的影响 慢性血管炎症的可溶性标记物，我们给 17β-雌二醇对绝经后妇女的影响 连接和结合循环的细胞黏附分子 炎性细胞进入血管壁。20名妇女参加了 随机开始为期一个月的透皮治疗 每天17β-雌二醇0.1毫克(9名女性)或17β-雌二醇0.1毫克 和甲孕酮2.5毫克每日(11名妇女)。我们 检测可溶性E-选择素、细胞间黏附分子 (ICAM-1)和血管细胞黏附分子(VCAM-1) 血清中的浓度和低密度的可氧化性 从血浆中分离的脂蛋白(分光光度法双烯 形成试验)在基线和治疗一个月后， 所有的检测都是盲目的。激素疗法 显著延长低密度脂蛋白的发病时间 氧化与预处理值的比较(77+/-13至88+/-16 Min，p=0.003)，并略微降低了最大速率 氧化(p=0.077)。激素治疗显著降低 ICAM-1水平下降8%(p=0.009)，并有降低E-选择素的趋势 VCAM-1水平下降6%(p=.084)。 联合服用醋酸甲羟孕酮没有显示 E-选择素的相对变化有任何显著差异， ICAM-1和VCAM-1水平，与单独17β-雌二醇组比较 (所有p&lt；.10)。我们得出结论，激素疗法具有良好的疗效。 对血管炎症标志物的影响，可能的变化 降低绝经后女性患冠状动脉疾病的风险。