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

项目摘要 尽管影响1/10的育龄妇女，子宫内膜异位症的诊断延迟7年， 症状的出现在非西班牙裔黑人（NHB）妇女中，尽管有类似的患病率， 子宫内膜异位症，它是诊断不足，由于无数的因素，包括子宫内膜异位症相关的报告 偏见，医疗差距，以及NHB妇女和医疗保健提供者之间的隐性偏见。这些 因素可能有助于NHB妇女被诊断为子宫内膜异位症的可能性是一半， 非西班牙裔白色（NHW）女性。重要的是，这意味着当NHB妇女确实接受子宫内膜异位症时， 如果没有诊断，它往往是在以后的生活中，导致进一步的疾病进展和更严重的疾病。鉴于 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 可能导致在该人群中观察到的CVD发病率和死亡率增加。NHB女性 心血管疾病的发病率不成比例地更高，与NHW同行相比，总体结果更差。 由于母基金的目的是分解炎症和氧化应激在早期糖尿病中的作用， 子宫内膜异位症女性CVD的表现，首先了解种族相关的差异是至关重要的 这些病理生理状态的基础。因此，为这种多样性补充拟议的研究 将系统地询问内皮和微血管功能中与种族相关的差异， 至关重要的基础，以告知家长补助金，使我们能够有效地考虑种族作为一个变量， 总体研究。我们将检验健康的非西班牙裔黑人中内皮功能受损的假设， (NHB)与非西班牙裔白色（NHW）女性相比，使用 安慰剂对照设计中系统性敲低核因子κ B细胞（NF-κB）的稳健方法 (oral双水杨酸酯），将在微循环中评估内皮功能（激光多普勒血流仪耦合 皮内微透析）和大循环（肱动脉血流介导的血管舒张; FMD）。 外周血单个核细胞（PBMC）中的特异性免疫细胞测定将提供离体证据， 支持功能性血管研究。这一补充将提供生物医学研究的培训， 来自不同背景的合格候选人。

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.