High Dimensional Cytometric Assay for Clinical Assessment of Vascular Health

描述（由申请人提供）：动脉粥样硬化疾病是一种流行的进行性疾病，在亚临床阶段难以评估。一个发展中的和令人兴奋的生物标志物的策略是测量微粒（MP）和评估循环祖细胞和成熟内皮细胞。所有的真核细胞都会在激活或凋亡时释放MP。血浆MP的升高，特别是内皮源性MP的升高，反映了细胞损伤，并且是血管功能障碍的替代标志物。MP已经在血管功能障碍和炎症是重要病理生理机制的许多病症中被列举，例如冠状动脉疾病或血栓性微血管病。我们最近完成了一项初步研究，评估糖尿病患者的MP水平，并将流式细胞术结果与非细胞特异性酶联免疫吸附试验（ELISA）结果进行了比较。ELISA测定结果与流式细胞术结果相关，但不能区分微粒来源的细胞。Cytovas的总体目标是开发和验证一种新型的高通量，高含量，流式细胞术检测，使用独特的生物计算方法，将测量细胞和亚细胞，为心血管风险个体提供签名。对于这项研究，我们将通过以下具体目标开发MP组件：1）使用流式细胞术优化MP的可重复检测程序; 2）推导出用于临床实施的计算分析范式。这种高通量、高信息含量的方法可能被证明在临床上可用于对患者的心血管风险进行分层，指导和监测对治疗的反应，以及开发新的治疗和预防方法。

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.