Drug abuse and HIV-associated pulmonary vascular injury

药物滥用和 HIV 相关肺血管损伤

• 批准号: 10799336
• 负责人: Navneet Kaur Dhillon
• 金额: $ 30.21万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10799336
• 关键词: Acceleration; Administrative Supplement; Age; Aging; Aorta; Apoptosis; Award; Biological Assay; Biological Markers; Blood Vessels; Cardiopulmonary; Cardiovascular Diseases; Cell Aging; Cell Communication; Cells; Clinical; Clinical Research; Clinical Trials; Communicable Diseases; Complication; Critical Care; Data; Data Analyses; Development; Diagnostic tests; Disease; Drug abuse; Echocardiography; Endothelial Cells; Endothelium; Functional disorder; Future; Gender; General Population; HIV; Health; Human; Individual; Infection; Inflammatory; Kidney; Laboratories; Libraries; Light; Link; Lung; Mediating; Mediator; Microfluidic Microchips; Microfluidics; Molecular; Myocardial dysfunction; Nanochip Analytical Device; Parents; Pathology; Patients; Persons; Phenotype; Physicians; Physiological; Plasma; Premature aging syndrome; Prevalence; Procedures; Proteins; Proteomics; Publishing; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Heart Disease; Pulmonary Hypertension; Pulmonary artery structure; Pulmonary function tests; Reporting; Research Personnel; Risk Factors; Role; Science; Scientist; Smooth Muscle; Smooth Muscle Myocytes; Specificity; Technology; Testing; Therapeutic Intervention; Translational Research; United States National Institutes of Health; Untranslated RNA; Vascular Diseases; Vascular Endothelial Cell; accurate diagnostics; biomarker identification; cell type; cerebrovascular; clinical practice; cohort; comorbidity; cost effective; detection platform; experience; extracellular vesicles; frailty; holistic approach; innovation; lung vascular injury; nanoengineering; novel; novel therapeutic intervention; potential biomarker; preventive intervention; protective effect; pulmonary vascular cells; pulmonary vascular disorder; response; screening; senescence; user-friendly; vascular injury

Project Summary This administrative supplement proposal is to examine if the circulating endothelial-derived small extracellular vesicles (EVs) can be leveraged as a non-invasive biomarker of pulmonary vascular dysfunction using a novel microfluidic chip-based platform. Lately, EVs have emerged as important mediators in cell-cell communication, and the role of alterations in their cargo has been implicated in various diseases, including pulmonary hypertension (PH). However, to allow for rapid integration into clinical practice, there remains a need for an inexpensive, user-friendly approach to the quantitative analysis of EV-linked putative biomarkers. So, in this supplement, we intend to leverage a novel microfluidics-based bioanalytical platform to overcome these technological barriers and the procedure complexity of isolating EVs required for screening large patient cohorts. Premature aging is one of the important factors contributing to the increased prevalence of cardiopulmonary diseases in people living with HIV (PWH) and pulmonary vascular endothelial cells have been reported to be highly senescent in PH. Using a highly sensitive nanoengineered chip-based bioanalytic platform for the detection of EC-EVs and a targeted proteomics approach, we propose to test the central hypothesis that the higher numbers of circulating endothelial-derived small EVs (EC-EVs) in PWH carry pro- aging factors that are associated with an increased prevalence of HIV associated PH. This supplement request is within the scope of an active parent NIH award on HIV-PH, and the innovative microfluidic approach is expected to expedite the analysis of a selective sub-population of plasma-derived EVs with increased sensitivity, specificity, and efficiency. This state-of-the-art technology will also allow for future customization of new putative EV-linked biomarkers in larger clinical studies. Furthermore, this technology may be adapted in the future to also identify markers of other vascular pathologies such as frailty and cerebrovascular and renal pathologies, which are very common in PWH.

项目摘要 本管理补充提案旨在检查循环内皮源性小 细胞外囊泡（EV）可作为肺血管功能障碍的非侵入性生物标志物 使用一种新的微流控芯片平台。近年来，EV已成为细胞-细胞免疫调节的重要介质。 交流，以及货物的改变在各种疾病中的作用，包括 肺动脉高压（PH）。然而，为了允许快速整合到临床实践中， 需要一种廉价的，用户友好的方法来定量分析EV相关的推定生物标志物。 因此，在本补充中，我们打算利用一种新的基于微流体的生物分析平台来克服 这些技术障碍和隔离EV的程序复杂性需要筛查大病人 同伙过早衰老是导致老年痴呆症发病率增加的重要因素之一。 HIV感染者的心肺疾病（PWH）和肺血管内皮细胞已经被 据报道，在PH中高度衰老。使用高度灵敏的基于纳米工程芯片的生物分析 平台检测EC-EV和有针对性的蛋白质组学方法，我们建议测试中央 假设PWH中循环内皮源性小EV（EC-EV）的数量较高， 老龄化因素与艾滋病毒相关PH的患病率增加有关。本补充要求 属于美国国立卫生研究院（NIH）关于HIV-PH的活跃母奖的范围，而创新的微流体方法是 预计将加快对血浆衍生EV的选择性亚群的分析， 灵敏度、特异性和效率。这种最先进的技术还将允许未来定制 在更大规模的临床研究中发现新的推定EV相关生物标志物。此外，该技术可以适用于 未来还将确定其他血管病变的标志物，如虚弱、脑血管和肾脏 这些病症在威尔斯亲王医院非常常见。