Sex differences in the role of multi-omicsin HIV-associated carotid artery atherosclerosis

多组学在 HIV 相关颈动脉粥样硬化中作用的性别差异

• 批准号: 10656874
• 负责人: Gypsyamber D'Souza
• 金额: $ 1.17万
• 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: 2019-04-09 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10656874
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Administrative Supplement; Affect; Aging; Alcohol consumption; Area; Atherosclerosis; Bacteria; Bone Density; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Carotid Artery Plaques; Carotid Atherosclerotic Disease; Ceramides; Cessation of life; Chronic Disease; Cognition; Cohort Studies; Data; Databases; Detection; Development; Diabetes Mellitus; Drug usage; Estradiol; Estrogens; Etiology; Female; Functional disorder; Fusobacterium; Future; Gastrointestinal tract structure; Genetic Determinism; Genetic Transcription; Genomics; Gonadal Steroid Hormones; HIV; HIV Infections; Hepatitis C virus; Hormonal; Human; Human Microbiome; Imidazole; Immune; Immune System Diseases; Immunologic Markers; Impaired cognition; Indoles; Inflammation; Inflammatory; Integrase Inhibitors; Intervention; Knowledge; Kynurenine; Lead; Link; Lipids; Lipopolysaccharides; Longevity; Measurement; Measures; Mediating; Menopause; Mental Depression; Mental Health; Metabolic; Modification; Morbidity - disease rate; Obesity; Oral; Oral cavity; Outcome; Paper; Pathogenesis; Pathway interactions; Peptidoglycan; Persons; Phenotype; Play; Population; Prevention; Prevention strategy; Prophylactic treatment; Propionates; Psychosocial Stress; Research; Risk Factors; Role; Sex Differences; Shapes; Sleep; Stroke; Testosterone; Tissues; Tryptophan; United States National Institutes of Health; Viral; Volatile Fatty Acids; Woman; Work; arterial stiffness; biological specimen archives; biomarker panel; cardioprotection; cardiovascular disorder risk; clinical care; comorbidity; data centers; falls; gut microbiome; gut microbiota; hormone therapy; immune activation; immune function; insight; male; men; metabolome; metabolomics; microbial; microbiome; microbiota; mortality; multiple omics; novel; ovarian reserve; routine practice; sex disparity; social health determinants; treatment strategy; trimethyloxamine; ultrasound

MACS/WIHS Combined Cohort Study (MWCCS) Administrative Supplement: Abstract. While significant recent changes in the clinical care of people with HIV (PWH) (e.g., universal ART initiation, greater use of statins as prophylaxis) have reduced cardiovascular disease (CVD) risk, concurrent developments that may increase CVD risk (e.g., shift to integrase inhibitors as first-line HIV treatment, continued aging of the HIV population) mean that the determinants of CVD in PWH are ever-changing. We have the opportunity to extend our existing MWCCS database of -omics measures in women in relation to HIV-associated CVD to men, and expand the scope with additional assessments of the microbiome, metabolome, and sex hormones. We propose to use archived specimens to measure gut microbiota and selected microbiome-related metabolites and immune marker panels, including markers of immune activation, gut barrier dysfunction and microbial translocation in relation to carotid atherosclerosis in MWCCS men, and assess both the independent and mediating roles of sex hormones in this relationship among both women and men with HIV. Our aims support HIV/AIDS research that falls under the following NIH high priority AIDS-designated topics: 1) immune dysfunction, persistent inflammation, and microbiome and genetic determinants that underpin the development of high priority HIV co-morbidities, and 2) long-term treatment or prevention strategies for HIV-relevant comorbid conditions across the lifespan.

MACS/WIHS 联合队列研究 (MWCCS) 行政补充： 抽象的。虽然艾滋病毒感染者 (PWH) 的临床护理最近发生了重大变化（例如， 普遍的 ART 启动、更多地使用他汀类药物作为预防）减少了心血管疾病 疾病 (CVD) 风险、可能增加 CVD 风险的并发发展（例如，转移到 整合酶抑制剂作为一线艾滋病毒治疗，艾滋病毒人口持续老龄化）意味着 产后卫生保健中 CVD 的决定因素不断变化。我们有机会扩展我们的 现有 MWCCS 数据库，其中包含与 HIV 相关的 CVD 相关的女性组学措施 男性，并通过对微生物组、代谢组和 性激素。我们建议使用存档的样本来测量肠道微生物群并选择 微生物组相关代谢物和免疫标记物组，包括免疫标记物 与颈动脉相关的激活、肠道屏障功能障碍和微生物移位 MWCCS 男性动脉粥样硬化，并评估性别的独立作用和中介作用 女性和男性艾滋病毒感染者之间的这种关系中的激素。我们的目标支持 属于以下 NIH 高优先级艾滋病指定主题的艾滋病毒/艾滋病研究：1) 免疫功能障碍、持续性炎症、微生物组和遗传决定因素 支持高度优先的艾滋病毒合并症的发展，以及 2) 长期治疗或 整个生命周期中与艾滋病毒相关的合并症的预防策略。