Drug abuse and HIV-associated pulmonary vascular injury

项目摘要 这项行政补充建议是检查循环内皮细胞衍生的小分子 细胞外小泡(EVS)可作为肺血管功能障碍的无创性生物标志物 使用一种新型的基于微流控芯片的平台。近来，电动汽车已成为细胞内重要的介体。 通信，其货物中的改装所起的作用与各种疾病有关，包括 肺动脉高压(PH)。然而，为了允许快速整合到临床实践中，仍然有一个 需要一种廉价、用户友好的方法来定量分析与肠道病毒相关的推定生物标志物。 因此，在这份补充材料中，我们打算利用一种新的基于微流控的生物分析平台来克服 这些技术障碍以及筛查大患者所需的分离EVS的程序复杂性 一群人。过早衰老是导致糖尿病患病率上升的重要因素之一。 艾滋病病毒携带者的心肺疾病和肺血管内皮细胞 据报道，在PH中高度衰老。利用高度敏感的纳米工程芯片进行生物分析 对于EC-EVS的检测平台和靶向蛋白质组学方法，我们建议测试中央 假设PWH中循环内皮源性小EV(EC-EVS)的数量较高，有利于 与HIV相关PH患病率增加相关的老龄化因素。这项补充要求 在美国国立卫生研究院关于HIV-PH的有效父母奖的范围内，创新的微流控方法是 预计将加快对等离子体衍生电动汽车的选择性亚群的分析， 灵敏度、特异度和效率。这项最先进的技术还将允许未来定制 在更大的临床研究中推定与EV相关的新生物标记物。此外，这项技术可能会被应用于 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 病理，这在PWH中非常常见。

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.