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

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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.