Understanding the role of estrogen receptor expression in CVD risk in women with and without HIV

了解雌激素受体表达在感染和未感染 HIV 的女性 CVD 风险中的作用

• 批准号: 10630208
• 负责人: Caitlin Moran
• 金额: $ 17.94万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10630208
• 关键词: Acceleration; Affect; Age; Aging; Antiinflammatory Effect; Antioxidants; Automobile Driving; Award; Binding; Biological Markers; Biology; Blood Vessels; Cardiac; Cardiovascular Diseases; Carotid Arteries; Cells; Centers of Research Excellence; Clinical; Clinical Research; Cohort Studies; Communicable Diseases; Data; Data Analyses; Disease; Disease Progression; ESR1 gene; ESR2 gene; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogen Receptors; Estrogens; Fibrosis; Foundations; Gene Expression; General Population; Gonadal Steroid Hormones; HIV; HIV Infections; HIV Seronegativity; HIV/AIDS; Immune; Immune System Diseases; Immune system; Inflammation; Inflammatory; Ischemic Stroke; Laboratories; Link; Macrophage Activation; Master of Science; Measures; Menopausal Status; Menopause; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; Myocardial Infarction; Myocardial Ischemia; Natural Immunity; Organ; Participant; Pathogenesis; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Persons; Positioning Attribute; Premature Menopause; Premenopause; Prevalence; Process; Recruitment Activity; Relative Risks; Research; Research Personnel; Research Proposals; Research Training; Resources; Risk; Risk Factors; Role; Sampling; Scientist; Serum; Sex Differences; Specialized Center; Testing; Thick; Time; Training; Translations; Vasodilation; Viral; Visit; Woman; Women' s Interagency HIV Study; Work; antiretroviral therapy; arterial stiffness; cardioprotection; cardiovascular disorder risk; cardiovascular risk factor; career; carotid intima-media thickness; cohort; design; early experience; endothelial dysfunction; experience; high risk; innovation; longitudinal analysis; men; primary outcome; prospective; protein expression; receptor; receptor expression; receptor function; recruit; secondary outcome; skills; training opportunity; translational scientist; trend; young woman

PROJECT SUMMARY/ABSTRACT With this K23 Mentored Patient-Oriented Research Career Development Award, I will develop the skills necessary to become an independent clinician-scientist focused on the pathogenesis of end-organ disease in women living with HIV (WLWH). My background in clinical Infectious Diseases and a Master of Science in Clinical Research have provided a foundation for this work, which will leverage the resources of the Atlanta Women’s Interagency HIV Study (WIHS) and Emory Specialized Center of Research Excellence (SCORE) on Sex Differences. During this Award, I will be mentored by Dr. Igho Ofotokun, an HIV translational researcher and PI of the Atlanta WIHS and SCORE, Dr. Gretchen Neigh, a basic scientist with experience in sex hormone biology, and Dr. Arshed Quyyumi, a cardiologist and researcher with extensive experience in translational vascular studies. I will complete advanced coursework in longitudinal data analysis, hands-on training in laboratory methods to measure estrogen receptor gene expression and translation, vascular function, and carotid artery wall thickness, and receive directed mentorship in CVD pathogenesis in women, sex hormone biology, and HIV clinical research. HIV is a risk factor for CVD, and young women living with HIV (WLWH) have an especially high risk for CVD compared to their HIV-uninfected counterparts. The mechanisms behind this phenomenon are poorly understood, but we postulate that differences in estrogen activity may play a role. Our prior work showed that CRP, a biomarker associated with CVD in the general population, does not predict subclinical CVD progression in WLWH, as it does in HIV-uninfected women, suggesting that there is a different mechanism driving the pathogenesis of CVD in WLWH, possibly related to estrogen activity. Estrogen affects inflammatory pathways via its interactions with estrogen receptor (ER) and ER, which are encoded by the genes ESR1 and ESR2, respectively. We found that the association between ESR1 and ESR2 expression on PBMCs and carotid intima-media thickness differs by age and HIV status in women in WIHS. We hypothesize that ESR1 and ESR2 expression and translation into ERα and ERβ is lower in WLWH than in HIV-negative women, and reduced ESR1 and ESR2 expression and translation are associated with greater subclinical CVD prevalence and progression. We propose a cohort study of virologically suppressed WLWH and at-risk HIV- negative women with the following aims: 1) To determine the effect of HIV infection in ESR1 and ESR2 expression and translation on PBMCs over time, 2) To determine if ESR1 and ESR2 expression and translation predicts prevalent subclinical CVD as measured by carotid artery wall thickness, endothelial dysfunction and arterial stiffness, and 3) To determine the association between ESR1 and ESR2 expression and translation in and subclinical CVD progression. Leveraging ongoing cohort studies that are actively recruiting will greatly enhance the feasibility of these aims. Completion of these aims will separate me scientifically from my mentors and position me to transition to independence as a clinician-scientist.

项目总结/文摘

项目成果

T-Cell Immune Dysregulation and Mortality in Women With Human Immunodeficiency Virus.

感染人类免疫缺陷病毒的女性 T 细胞免疫失调和死亡率。

• DOI: 10.1093/infdis/jiab433
• 发表时间: 2022
• 期刊: The Journal of infectious diseases
• 作者: Peters,BrandilynA;Moon,Jee-Young;Hanna,DavidB;Kutsch,Olaf;Fischl,Margaret;Moran,CaitlinA;Adimora,AdaoraA;Gange,Stephen;Roan,NadiaR;Michel,KatherineG;Augenbraun,Michael;Sharma,Anjali;Landay,Alan;Desai,Seema;Kaplan,Robert
• 通讯作者: Kaplan,Robert