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.
This proposal will provide a new way to manage healthcare for people with, or at risk of, certain heart and blood vessel diseases (such as atherosclerosis). Presently, healthcare for these people relies on the development of symptoms, by which time options are limited. The product that will be developed here will help to evaluate risk before symptoms develop, guide treatment decisions, and assess response to treatment.
