Mechanisms and interventions addressing accelerated cardiovascular disease risk in women with endometriosis

解决子宫内膜异位症女性心血管疾病风险加速的机制和干预措施

基本信息

批准号：
10838754
负责人：
Lacy M. ALEXANDER
金额：
$ 3.72万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-15 至 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10838754
关键词：
Acceleration Address Age Atherosclerosis Beta Cell Biomedical Research Blood Vessels Cardiovascular Diseases Cardiovascular Manifestation Cardiovascular system Cause of Death Cellular Assay Chronic Coupled Cutaneous Diagnosis Disease Disease Progression Endometrium Endothelium Estrogens Foundations Gynecologic Health Health Personnel Immune Impairment Infertility Inflammation Inflammation Mediators Inflammatory Inhibition of NF-KB activation Interleukin-1 beta Interleukin-6 Intervention Laboratories Laser-Doppler Flowmetry Lectin Life Link Mediating Microcirculation Microdialysis Modeling Morbidity - disease rate NF-kappa B Nature Nitric Oxide Not Hispanic or Latino Oral Outcome Oxidative Stress Pain Peripheral Blood Mononuclear Cell Placebo Control Population Predisposition Prevalence Prognosis Protocols documentation Qualifying Race Reporting Research Role Signal Transduction Site Symptoms TNF gene Testing Tissues Training Uterine cavity Vascular Diseases Vascular Endothelium Vasodilation Woman Work black women brachial artery cardiovascular disorder risk career development chronic pelvic pain comorbidity cytokine design dimer disease diagnosis disorder risk effective intervention endometriosis endothelial dysfunction experience health care disparity implicit bias improved knock-down mortality oxidized LDL receptors oxidized lipid p65 parent grant receptor reproductive response salicylsalicylic acid symptomatology systemic inflammatory response

项目摘要

PROJECT SUMMARY Despite impacting 1 in 10 women of reproductive age, endometriosis has a delay in diagnosis of 7 years from the onset of symptoms. In Non-Hispanic Black (NHB) women, despite having a similar prevalence of endometriosis it is underdiagnosed due to a myriad of factors, including symptomatology-related reporting biases, healthcare disparities, and implicit biases among both NHB women and healthcare providers. These factors may contribute to NHB women being half as likely to be diagnosed with endometriosis as compared to Non-Hispanic White (NHW) women. Importantly, this means that when NHB women do receive an endometriosis diagnosis, it tends to be later in life resulting in further disease progression and worse prognoses. Given the increased risk of cardiovascular disease risk in women with endometriosis, the delayed treatment in NHB women may contribute to the increase in morbidity and mortality from CVD observed in this population. NHB women have disproportionately higher rates of CVD and overall poorer outcomes compared to their NHW counterparts. As the parent grant aims to disaggregate the roles of inflammation and oxidative stress contributing to early manifestations of CVD in women with endometriosis, it is critical to first understand the race-related differences that underlying these pathophysiological states. Therefore, the proposed studies for this diversity supplement will systematically interrogate race-related differences in endothelial and microvascular function, providing a crucial foundation to inform the parent grant and allow us to effectively account for race as a variable in the overarching study. We will test the hypothesis that impaired endothelial function in healthy non-Hispanic Black (NHB) women relative to non-Hispanic White (NHW) women is mediated by inflammatory mechanisms. Using a robust approach to systemically knockdown nuclear factor kappa B cells (NF-κB) in a placebo control design (oral salsalate), endothelial function will be assessed in the microcirculation (laser Doppler flowmetry coupled with intradermal microdialysis) and the macrocirculation (brachial artery flow-mediated vasodilation; FMD). Specific immune cell assays in peripheral blood mononuclear cells (PBMCs) will provide ex vivo evidence to support of functional vascular studies. This supplement will provide training in biomedical research for a highly qualified candidate from a diverse background.

项目概要尽管影响十分之一的育龄妇女，但子宫内膜异位症的诊断延迟了 7 年。在非西班牙裔黑人 (NHB) 女性中，尽管其患病率相似，子宫内膜异位症由于多种因素而未被充分诊断，包括症状相关的报告 NHB 女性和医疗保健提供者之间的偏见、医疗保健差异和隐性偏见。一些因素可能导致 NHB 女性被诊断出子宫内膜异位症的可能性比男性低一半重要的是，这意味着当 NHB 女性确实患有子宫内膜异位症时。诊断往往会在晚年进行，导致疾病进一步进展和预后更差。子宫内膜异位症女性心血管疾病风险增加，NHB 女性延迟治疗可能导致该人群中观察到的 CVD 发病率和死亡率增加。与 NHW 捐赠者相比，他们的 CVD 发生率要高得多，而且总体预后较差。由于家长资助的目的是分解炎症和氧化应激在早期子宫内膜异位症女性的 CVD 表现，首先了解种族相关的差异至关重要因此，拟议的研究对这种多样性进行了补充。将系统地询问内皮和微血管功能中与种族相关的差异，提供告知家长补助金的重要基础，并使我们能够有效地将种族作为变量我们将检验健康非西班牙裔黑人内皮功能受损的假设。 (NHB) 女性相对于非西班牙裔白人 (NHW) 女性的炎症机制是通过炎症机制介导的。在安慰剂对照设计中系统性敲低核因子 kappa B 细胞 (NF-κB) 的稳健方法（口服水杨酸），将在微循环中评估内皮功能（激光多普勒血流计耦合皮内微透析）和大循环（肱动脉血流介导的血管舒张；FMD）。外周血单核细胞 (PBMC) 中的特异性免疫细胞检测将为以下方面提供离体证据：该补充品将为功能性血管研究提供高度培训。来自不同背景的合格候选人。