Effects of marijuana use on inflammation and vascular injury in adults with HIV infection

吸食大麻对成人艾滋病毒感染者炎症和血管损伤的影响

• 批准号: 9883769
• 负责人: Dana H. Gabuzda
• 金额: $ 64.86万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9883769
• 关键词: Acquired Immunodeficiency Syndrome; Acrolein; Address; Adult; Age; Aldehydes; Antiinflammatory Effect; Antioxidants; Aromatic Polycyclic Hydrocarbons; Attenuated; Automobile Driving; Bioinformatics; Biological Assay; Biological Markers; Cannabinoids; Cardiovascular Diseases; Cardiovascular system; Cell Adhesion; Cell Culture Techniques; Chronic; Clinical; Clinical Data; Coagulation Process; Computer Models; Data; Data Set; Disease Marker; Disease Progression; Drug Metabolic Detoxication; Endothelium; Enzyme-Linked Immunosorbent Assay; Event; Experimental Models; Exposure to; Expression Profiling; Gene Expression; Gene Expression Profile; Goals; HIV; HIV Infections; Health; Immunologic Markers; In Vitro; Individual; Inflammasome; Inflammation; Inflammatory; Injury; Innate Immune Response; Lipid Peroxidation; Machine Learning; Marijuana; Marijuana Smoking; Mass Spectrum Analysis; Mediating; Mediator of activation protein; Modeling; Nicotine; Outcome; Oxidative Stress; Pathway interactions; Pattern; Peripheral Blood Mononuclear Cell; Plasma; Population; Process; Prospective cohort; Proteomics; Risk Factors; Role; Safety; Sampling; Smoke; Smoker; Smoking; Testing; The Multicenter AIDS Cohort Study; Therapeutic Intervention; Time; Tobacco; Tobacco smoke; Tobacco smoking behavior; Toxic effect; Urine; cardiovascular risk factor; cohort; combustion product; comorbidity; immune activation; liquid chromatography mass spectrometry; marijuana smoke; marijuana use; men; metabolomics; middle age; monocyte; network models; neutrophil; predictive modeling; predictive test; response; therapeutic development; therapeutic target; tobacco exposure; transcriptome; vascular inflammation; vascular injury; volatile organic compound

Project Summary The goal of this proposal is to characterize biomarkers of marijuana smoke exposure in ART-treated HIV+ adults over age 40, and their relationship to inflammation and vascular injury in heavy users. Marijuana and tobacco smoking are both prevalent among HIV+ populations, but their individual and combined impacts on inflammation and cardiovascular risk are unknown. Preliminary studies using longitudinal data from a prospective cohort showed that chronic heavy marijuana smoking has no significant effect on HIV disease markers, but is associated with increased rates of incident cardiovascular events in ART-treated HIV+ men age 40-60 independently of tobacco smoking and traditional risk factors. Furthermore, we showed that heavy marijuana and/or tobacco smoking was associated with elevated WBC and neutrophil counts, immune activation, inflammation, and vascular injury in ART-treated HIV+ smokers. We hypothesize that specific combustion products in marijuana and tobacco smoke, including acrolein, other reactive aldehydes, and VOCs, can induce proinflammatory responses mediated through activated neutrophils and monocytes that promote chronic inflammation in ART-treated adults, contributing to cardiovascular risk by promoting lipid peroxidation, coagulation, vascular inflammation, and endothelial injury, while attenuating protective responses. We further hypothesize that these effects are additive upon dual exposure to both marijuana and tobacco smoke and augmented by HIV infection. To address these questions, we will use clinical samples and data from well- characterized longitudinal HIV+ cohorts to characterize marijuana smoke exposure biomarkers in plasma and urine samples and their relationship to inflammation, oxidative stress, and vascular injury. Bioinformatics, computational modeling, and cell culture models will be used to build and test models to explain the effects of specific constituents of marijuana smoke on inflammatory pathways, and how these pathways are modified in the setting of HIV infection. These studies will provide information that helps to explain chronic inflammation and elevated cardiovascular risk in ART-treated HIV+ adults, safety profiles of smoked cannabinoids, and potential strategies for therapeutic intervention.

项目总结