High Dimensional Cytometric Assay for Clinical Assessment of Vascular Health

描述(由申请人提供)：动脉粥样硬化性疾病是一种流行的进行性疾病，在亚临床阶段很难评估。一个发展中的和令人兴奋的生物标记物策略是测量微粒(MP)和评估循环中的祖细胞和成熟的内皮细胞。所有真核细胞在激活或凋亡时都会释放MPS。血浆MPS升高，尤其是内皮来源的MPS升高，反映了细胞损伤，是血管功能障碍的替代标志。MPS被列举在血管功能障碍和炎症是重要的病理生理机制的许多情况下，例如冠状动脉疾病或血栓性微血管病变。我们最近完成了一项初步研究，评估了糖尿病患者的MPS水平，并将流式细胞术的结果与非细胞特异性酶联免疫吸附试验(ELISA)的结果进行了比较。酶联免疫吸附试验检测结果与流式细胞仪检测结果相关，但没有区分微粒子的来源细胞。Cytovas的总体目标是利用一种独特的生物计算方法，开发和验证一种新型的高通量、高含量的流式细胞仪分析方法，该方法将测量细胞和亚细胞，为心血管风险个体提供特征。在这项研究中，我们将通过以下具体目标开发MP组件：1)完善使用流式细胞术检测MPS的可重复性检测程序；2)为临床实施提供计算分析范例。这种高通量、高信息含量的方法可能在临床上对患者的心血管风险分层、指导和监测治疗反应以及开发新的治疗和预防方法有用。

DESCRIPTION (provided by applicant): Atherosclerotic disease is a prevalent and progressive condition that can be difficult to assess during sub- clinical stages. A developing and exciting biomarker strategy is the measurement of microparticles (MPs) and assessment of circulating progenitor and mature endothelial cells. All eukaryotic cells shed MPs in response to activation or apoptosis. Elevation of plasma MPs, particularly those of endothelial origin, reflect cellular injury and is a surrogate marker for vascular dysfunction. MPs have been enumerated in a number of conditions where vascular dysfunction and inflammation are important pathophysiological mechanisms, for example coronary artery disease or thrombotic microangiopathies. We recently completed a pilot study evaluating levels of MPs in patients with diabetes mellitus and compared flow cytometry results with those of a non cell specific Enzyme Linked ImmunoSorbent assay (ELISA). The ELISA assay results correlated with flow cytometry results but did not distinguish the cell of origin where the micoparticle originated. Cytovas' overall goal is to develop and validate a novel highthroughput, high content, flow cytometric assay, using a unique biocomputational approach, that will measure cellular and subcellular that provide a signature for individuals at cardiovascular risk. For this study, we will develop the MP component via the following specif aims: 1) Refine the procedures for reproducible detection of MPs using flow cytometry; and 2) Derive a computational analysis paradigm for clinical implementation. Such a high throughput, high information content approach may prove clinically useful for stratifying cardiovascular risk among patients, in guiding and monitoring response to therapy, and in developing new therapeutic and preventive approaches.