Emerging factors in the pathophysiology of endothelial dysfunction in HIV+ women

艾滋病毒女性内皮功能障碍病理生理学的新因素

• 批准号: 10570853
• 负责人: Allison G Hays
• 金额: $ 28.35万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10570853
• 关键词: Abdomen; Acceleration; Adipose tissue; Affect; Age; Age Factors; Atherosclerosis; Biological Markers; Body Composition; Cardiac; Cardiovascular Diseases; Cardiovascular system; Catheterization; Cause of Death; Cessation of life; Cholesterol Homeostasis; Chronic; Clinical; Clinical Research; Coronary; Coronary Arteriosclerosis; Coronary artery; Data; Depressed mood; Development; Disease; Endothelium; Estrogens; Event; Experimental Models; Functional disorder; Funding; Future; General Population; Gonadal Steroid Hormones; HIV; HIV Infections; Heart Diseases; Hematological Disease; Hormonal; Imaging Techniques; Impairment; Individual; Inflammation; Inflammatory; Intervention; Intervention Studies; Knowledge; Link; Liver; Longevity; Magnetic Resonance Imaging; Measures; Mediating; Mediator; Medical; Menopause; Metabolic; Methods; Myocardial Infarction; Obesity; Observational Study; Pathway interactions; Peptide Hydrolases; Perimenopause; Persons; Play; Population; Premenopause; Prevalence; Process; Prognostic Marker; Proprotein Convertases; Reporting; Reproducibility; Risk; Risk Factors; Role; Sex Differences; Subtilisins; Testing; Testosterone; Therapeutic Intervention; Time; Vascular Diseases; Visceral; Woman; Work; antiretroviral therapy; atherogenesis; cardiovascular disorder risk; cardiovascular risk factor; coronary plaque; cytokine; design; endothelial dysfunction; experience; heart disease risk; high risk population; immune activation; inflammatory marker; insight; lipid metabolism; men; mullerian-inhibiting hormone; non-invasive imaging; novel; ovarian reserve; paracrine; prevent; sex; source localization; systemic inflammatory response

Human immunodeficiency virus positive (HIV+) individuals are living longer with antiretroviral therapy (ART) but are now experiencing coronary artery disease (CAD) as an important cause of death, especially as they age. Because this CAD is not well explained by conventional CAD risk factors, we hypothesize that changes that occur in body composition in HIV result in increased metabolically-active visceral adipose tissue (VAT) in the abdomen and around the coronary arteries (epicardial adipose tissue: EAT) that releases inflammatory cytokines contributing systemically and locally to the fundamental processes accelerating CAD in HIV+ individuals. The increased local inflammation resulting from EAT may contribute to the process of coronary endothelial dysfunction which plays a critical role in the progression and clinical manifestations of CAD, and is a marker for sub-clinical disease, an independent predictor of adverse cardiac events, and a potential target for medical interventions. Moreover in HIV+ women other factors may be important in endothelial dysfunction such as a reduced ovarian reserve and other hormonal abnormalities that commonly affect women with HIV. We recently developed noninvasive, reproducible MRI-based methods to measure coronary endothelial function (CEF). This new ability to noninvasively evaluate CEF offers a means to probe mechanisms contributing to CAD pathophysiology HIV+ women and men. We propose in this application to determine 1) whether CEF and markers of inflammation and EAT are inversely related in HIV + people, 2) whether this relationship differs in women compared with men living with HIV and 3) whether reduced ovarian reserve is associated with endothelial abnormalities in HIV+ women. We will determine in HIV+ people whether reduced CEF can be explained, at least in part, by increased inflammation. Together these studies will offer new pathophysiologic insights into HIV-associated vascular disease, and how the pathophysiology may differ between women and men living with HIV. These studies are critical first steps to better understanding sex-differences in vascular disease that develops commonly in HIV. The proposed study is clinically feasible in the proposed time period, and could be used to design future therapeutic intervention studies, and may offer a fundamentally new understanding of the most important contributing factors of endothelial dysfunction in HIV.

人类免疫缺陷病毒阳性（HIV+）个体的抗逆转录病毒寿命更长 治疗（ART），但现在正在经历冠状动脉疾病（CAD）作为死亡的重要原因， 特别是随着年龄的增长。因为常规CAD风险因素对此CAD没有很好地解释，所以我们 假设HIV中人体成分发生的变化导致代谢增加 腹部和冠状动脉周围的内脏脂肪组织（增值税）（心外膜脂肪 组织：吃）释放炎症细胞因子在全身和局部促进基本的促进性细胞因子 在HIV+个体中加速CAD的过程。饮食引起的局部炎症增加 可能有助于冠状动脉内皮功能障碍的过程，该过程在 CAD的进展和临床表现，是亚临床疾病的标记，一种独立的 预测不良心脏事件，以及医疗干预措施的潜在目标。此外，艾滋病毒+ 女性其他因素在内皮功能障碍中可能很重要，例如减少卵巢储备和 通常影响艾滋病毒女性的其他激素异常。我们最近开发了 非侵入性，基于MRI的可再现方法测量冠状动脉内皮功能（CEF）。这个新 非侵入性评估CEF的能力提供了一种探测有助于CAD的机制的方法 病理生理艾滋病毒+男性和男性。我们在此应用中建议确定1）CEF是否 在艾滋病毒 +人中，炎症和饮食的标记成反比，2）这种关系是否关系 与艾滋病毒携带的男性相比，女性的不同和3）卵巢储备是否减少 与艾滋病毒+妇女的内皮异常相关。我们将在艾滋病毒+人中确定是否 减少的CEF可以至少部分通过增加的炎症来解释。这些研究将共同 为与HIV相关的血管疾病提供新的病理生理学见解，以及如何病理生理学 艾滋病毒感染的男女可能有所不同。这些研究是更好的第一步 了解通常在艾滋病毒中发展的血管疾病的性别差异。拟议的研究是 在拟议的时间段内临床上可行，可用于设计未来的治疗干预措施 研究，并可能从根本上对最重要的因素有了新的了解 艾滋病毒中的内皮功能障碍。

项目成果

Imaging Assessment of Endothelial Function: An Index of Cardiovascular Health.

• DOI: 10.3389/fcvm.2022.778762
• 发表时间: 2022
• 期刊: Frontiers in cardiovascular medicine
• 影响因子: 3.6

Visceral adiposity, muscle composition, and exercise tolerance in heart failure with preserved ejection fraction.

• DOI: 10.1002/ehf2.13382
• 发表时间: 2021-08
• 期刊: ESC heart failure
• 影响因子: 3.8
• 作者: Ying W;Sharma K;Yanek LR;Vaidya D;Schär M;Markl M;Subramanya V;Soleimani S;Ouyang P;Michos ED;Shah SJ;Hays AG
• 通讯作者: Hays AG

Unsupervised machine learning demonstrates the prognostic value of TAPSE/PASP ratio among hospitalized patients with COVID-19.

• DOI: 10.1111/echo.15432
• 发表时间: 2022-09
• 期刊: ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES
• 影响因子: 1.5
• 作者: Jani, Vivek;Kapoor, Karan;Meyer, Joseph;Lu, Jim;Goerlich, Erin;Metkus, Thomas S.;Madrazo, Jose A.;Michos, Erin;Wu, Katherine;Bavaro, Nicole;Kutty, Shelby;Hays, Allison G.;Mukherjee, Monica
• 通讯作者: Mukherjee, Monica

Rapid Improvement of Coronary Endothelial Function With PCSK9 Inhibition in People With HIV Is Associated With Reduced Lipoprotein (a) and Not LDL-cholesterol.

HIV 感染者通过抑制 PCSK9 快速改善冠状动脉内皮功能与脂蛋白 (a) 降低有关，而不是与 LDL 胆固醇降低有关。

• DOI: 10.1161/circimaging.123.015693
• 发表时间: 2023
• 期刊: Circulation. Cardiovascular imaging
• 作者: Harb,Tarek;Ziogos,Efthymios;Schär,Michael;Brown,ToddT;Lai,Shenghan;Gerstenblith,Gary;Hays,AllisonG;Leucker,ThorstenM
• 通讯作者: Leucker,ThorstenM