Stress, Vascular Function, and Inflammation as Mechanisms of Sex Differences in Cardiovascular Risk

压力、血管功能和炎症是心血管风险性别差异的机制

基本信息

批准号：
10457199
负责人：
Samaah M Sullivan
金额：
$ 13.45万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-10 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10457199
关键词：
Acute myocardial infarction Adverse effects Age Age-Years Aging Arterial Fatty Streak Biological Markers Biology Blood Vessels Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cause of Death Clinical Contraceptive Usage Coronary heart disease Data Data Collection Development Discrimination Emotional Stress Enrollment Environmental Risk Factor Faculty Female Future Goals Gonadal Steroid Hormones Heart Diseases Hormone use Immune Immune response Impairment Infertility Inflammation Inflammatory Infrastructure Interleukin-6 Ischemia Laboratories Measures Mediating Menopausal Status Menopause Mental Depression Mentors Myocardial Infarction Myocardial Ischemia National Heart, Lung, and Blood Institute Outcome Ovarian Pathway interactions Physiology Pregnancy Histories Premenopause Prevention Prognosis Psyche structure Psychosocial Stress Recording of previous events Reporting Reproduction Reproductive History Research Research Project Grants Risk Risk Factors Role Sampling Severities Sex Differences Stress Stress Tests Training United States United States National Institutes of Health Woman Work aged atherosclerosis risk base biological adaptation to stress biological sex cardiovascular effects cardiovascular risk factor career career development diminished ovarian reserve early life adversity early onset emotional factor heart function men middle age mortality mullerian-inhibiting hormone neighborhood disadvantage older women ovarian dysfunction ovarian reserve participant enrollment premature psychosocial psychosocial stressors recruit response sexual dimorphism socioeconomic disadvantage stress reactivity training opportunity young woman

项目摘要

ABSTRACT The purpose of this K01 proposal is to facilitate the applicant's transition to an independent research career focused on stress and sex hormone biology to understand mechanisms of sex differences in cardiovascular disease and potential disparities among women. Training components for the proposed research will include direct clinical training in stress testing and vascular physiology, new training in sex hormones and measures of ovarian function, faculty career development, active mentoring, and completion of the proposed research. The premise of this research project is based on preliminary data from the applicant's own research which suggest that compared to men, women (and particularly, younger women) with coronary heart disease have distinct vascular mechanisms in relation to stress and myocardial ischemia, and have higher basal and stress-related inflammation. We have also reported that women ≤ 60 years of age are more likely to develop myocardial ischemia during mental stress than men of similar age. The underlying explanation for these sex differences is unknown; however, one potential mechanism involves sex hormone biology among premenopausal women and across the menopausal transition. Stress may impair female reproduction through diminished ovarian reserve and induce earlier age at menopause, which have been associated with cardiovascular risk, possibly through sex hormone-related pathways influencing immune response, vascular, and cardiac function. The overall goal of this project is to understand mechanisms for sex differences in inflammatory and vascular responses to mental stress, and the role of ovarian function and menopausal status among women. The applicant will leverage the infrastructure of the Myocardial Infarction and Mental Stress Study 2 (MIMS2: R01HL109413), which was recently renewed for a new enrollment wave (MIMS3: 2R01HL109413). The two waves will total 300 men and 300 women with a recent myocardial infarction (MI), ≤ 60 years of age. The applicant will add the collection of data on anti-Müllerian Hormone (AMH), a biomarker of ovarian reserve and menopausal status in women and examine AMH levels in relation to stress responses. The applicant will also recruit a sample of healthy women (n = 100) matched for age to the post-MI women, for comparison of AMH levels and age at menopause. The scientific aims of this project are to: 1) Examine sex differences in inflammation and vascular function at baseline and in response to mental stress and the role of gonadal aging by comparing young and middle-aged women and men; 2) Examine and compare inflammatory and vascular profiles and gonadal aging and age at menopause with age-matched control women; and 3) Examine whether psychosocial stressors such as depression, early life adversity, discrimination, and neighborhood disadvantage are associated with gonadal aging (lower AMH levels) in women with a recent MI and age matched controls. The new enrollment of patients and controls will provide key opportunities for training and data collection on gonadal aging and vascular function to inform the development of a future NIH-R01 proposal.

抽象的该K01提案的目的是促进申请人向独立研究职业的过渡专注于压力和性别同性生物学，以了解心血管中性别差异的机制妇女疾病和潜在差异。拟议研究的培训组件将包括胁迫测试和血管生理学，性激素的新训练以及测量的直接临床训练卵巢功能，教师职业发展，积极的心理以及拟议研究的完成。该研究项目的前提是基于申请人自己研究的初步数据与男性相比，患有冠心病的男性（尤其是年轻女性）具有不同的与压力和心肌缺血有关的血管机制，具有较高的基本和应力相关炎。我们还报告说，≤60岁的女性更有可能发展心肌精神压力期间的缺血比年龄相似的男性。这些性别差异的基本解释是未知;但是，一种潜在的机制涉及绝经前妇女的性激素生物学以及整个更年期的过渡。压力可能会通过减少的卵巢损害女性繁殖储备和诱导与心血管风险相关的绝经期的较早年龄通过性激素相关的途径影响免疫反应，血管和心脏功能。这该项目的总体目标是了解炎症和血管性别差异的机制对精神压力的反应，以及女性卵巢功能和更年期地位的作用。申请人将利用心肌违规和心理压力研究的基础设施2（MIMS2： R01HL109413），最近续签了新的入学浪潮（MIMS3：2R01HL109413）。两个波浪将总共有300名男性和300名女性，最近有心肌梗塞（MI）≤60岁。这申请人将添加有关抗穆勒激素（AMH）的数据收集，卵巢储备的生物标志物和女性的更年期地位并检查与压力反应有关的AMH水平。申请人也将招募年龄与MI后女性相匹配的健康女性样本（n = 100），以比较AMH 更年期的水平和年龄。该项目的科学目的是：1）检查性别差异基线时的炎症和血管功能以及响应精神压力和性腺衰老的作用通过比较年轻和中年男女； 2）检查和比较炎症和血管剖面和性腺衰老和更年期的年龄与年龄匹配的对照女性； 3）检查是否抑郁症，早期逆境，歧视和邻里灾难等社会心理压力源与近期MI和年龄匹配对照的女性中的性腺衰老（AMH水平较低）有关。患者和对照组的新入学将为培训和数据收集提供关键机会性腺衰老和血管功能，以告知未来NIH-R01提案的发展。