Sex Hormones and Pulmonary Vascular and Right Ventricular Dysfunction

性激素与肺血管和右心室功能障碍

基本信息

批准号：
8854115
负责人：
Corey E Ventetuolo
金额：
$ 27.04万
依托单位：
OCEAN STATE RESEARCH INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8854115
关键词：
Androgens Angiopoietins Animals Biological Markers Biology Blood Vessels Blood flow Brain natriuretic peptide Carbon Monoxide Cardiac Cardiopulmonary Case-Control Studies Centers of Research Excellence Cessation of life Clinical Research Cohort Studies Diffuse Discipline of obstetrics Disease Echocardiography Epidemiology Estradiol Estrogen Therapy Estrogens Exercise Failure Female Gender Role Gonadal Steroid Hormones Gynecologic Health Heart Atrium Hormonal Instruction Link Lung Luteal Phase Measurement Measures Menstrual cycle Myocardial Oral Contraceptives Outcome Pathway interactions Patients Phase Postmenopause Pregnancy Premenopause Prevalence Prevention strategy Pulmonary Hypertension Pulmonary artery structure Recording of previous events Registries Reporting Right Ventricular Dysfunction Right Ventricular Function Risk Risk Factors Serum Stem cells Variant Vascular Diseases Vascular Endothelial Growth Factors Ventricular Woman angiogenesis burden of illness cohort dehydroepiandrosterone hemodynamics hormone therapy improved indexing injury and repair innovation male men neovascularization physiologic model pill pleiotropism pressure prospective pulmonary arterial hypertension sex treatment strategy vascular bed

项目摘要

PROJECT SUMMARY (See instructions); Female sex is the best established risk factor for pulmonary arterial hypertension (PAH), yet women have preserved right ventricular (RV) function and survival compared to men with PAH. This so-called "estrogen paradox" is as yet unexplained. RV function determines outcome in disease, but the mechanisms and determinants of RV failure are unknown. We hypothesize that high estrogen states promote pulmonary vascular angiogenesis and RV myocardial collateral flow, resulting in pleiotropic effects on the pulmonary vasculature and the RV. In postmenopausal women, the hormonal mileu (e.g., sex hormone and estradiol [E2] metabolite levels) can be characterized; in premenopausal women the normal menstrual cycle (marked by a predictable spike in E2) provides a physiologic model to characterize these relationships. We propose: 1) a prospective cohort study (N=75) to determine whether the sex hormone milieu is associated with markers of angiogenesis (vascular endothelial growth factor [VEGF], angiopoietins [Ang], endothelial progenitor cells [EPCs]) and RV function assessed by hemodynamics in postmenopausal women wdth PAH and 2) a prospective case-control study (N = 40) to determine whether the menstrual cycle is associated with markers of angiogenesis (VEGF, Ang, EPCs) and RV function assessed by echocardiography in premenopausal women with PAH as compared to controls. We anticipate that in both pre and postmenopausal women, high E2 states will be associated with higher levels of angiogenesis markers but improved surrogates of RV function. The extent to which the influence of sex hormones on markers of angiogenesis and RV function can be defined is supported by 1) the use of separate studies to incorporate both pre and postmenopausal women and 2) the combination of a variety of carefully selected biomarkers aimed at both angiogenesis and RV function.

项目摘要（请参阅说明）；女性是肺动脉高压（PAH）的最佳建立危险因素，但与患有PAH的男性相比，女性保留了右心（RV）功能和存活率。这种所谓的“雌激素悖论”尚未解释。 RV功能决定了疾病的结果，但是RV衰竭的机制和决定因素尚不清楚。我们假设高雌激素状态促进肺血管血管生成和RV心肌侧支流，从而对肺血管和RV产生多效性。在绝经后妇女中，可以表征激素麦龙（例如，性激素和雌二醇[E2]代谢物水平）。在绝经前女性中，正常的月经周期（以E2中的可预测尖峰为标志）提供了一种生理模型来表征这些关系。我们提出：1）一项前瞻性队列研究（n = 75），以确定性激素环境与血管生成标志物（血管内皮生长因子[VEGF] [VEGF]，ANG [ANG]，内皮祖细胞[EPCS]）以及在较细胞的ROV功能和2个妇女的ROV功能相关的妇女和RV的功能，并在妇女妇女中评估了较高的妇女，（n = 40）确定月经周期是否与与对照组相比，在具有PAH的预兆月妇女中，通过超声心动图评估了通过超声心动图评估的血管生成标记（VEGF，ANG，EPC）和RV功能。我们预计，在绝经前和绝经后妇女中，高E2状态都将与较高的血管生成标记相关，但改善了RV功能的替代物。 1）使用单独的研究融合了绝经前和后妇女的使用，可以确定性激素对血管生成和RV功能标记的影响的程度，以及2）旨在使用血管生成和RV功能的各种精心选择的生物标志物组合。