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.

项目概要 该行政补充提案旨在检查循环内皮衍生的小分子是否 细胞外囊泡（EV）可用作肺血管功能障碍的非侵入性生物标志物 使用一种新颖的基于微流控芯片的平台。最近，电动汽车已成为细胞间的重要介质 通信及其货物的改变与多种疾病有关，包括 肺动脉高压（PH）。然而，为了快速融入临床实践，仍然存在 需要一种廉价、用户友好的方法来定量分析与 EV 相关的假定生物标志物。 因此，在本补充材料中，我们打算利用一种新型的基于微流体的生物分析平台来克服 这些技术障碍以及筛查大型患者所需的隔离 EV 的程序复杂性 队列。过早衰老是导致早衰患病率增加的重要因素之一 HIV 感染者 (PWH) 和肺血管内皮细胞的心肺疾病 据报道PH高度衰老。使用高度灵敏的基于纳米工程芯片的生物分析 为了检测 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 中循环内皮衍生的小 EV（EC-EV）数量较多，携带亲 与 HIV 相关 PH 患病率增加有关的衰老因素。此补充要求 属于 NIH 现行 HIV-PH 家长奖的范围，创新的微流体方法是 预计将加快对血浆衍生的 EV 的选择性亚群的分析，其增加 灵敏度、特异性和效率。这种最先进的技术也将允许未来的定制 更大型临床研究中新的推定 EV 相关生物标志物。此外，该技术可适用于 未来还可以识别其他血管病理学的标志物，例如虚弱、脑血管和肾脏疾病 病理，这在感染者医院中很常见。