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+）个体使用抗逆转录病毒后寿命延长

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

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

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