Department of Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Cytometry B Clin Cytom. 2013 Jul-Aug;84(4):255-66. doi: 10.1002/cyto.b.21095. Epub 2013 Jun 5.
An inexpensive and accurate blood test does not currently exist that can evaluate the cardiovascular health of a patient. This study evaluated a novel high dimensional flow cytometry approach in combination with cytometric fingerprinting (CF), to comprehensively enumerate differentially expressed subsets of pro-angiogenic circulating progenitor cells (CPCs), involved in the repair of vasculature, and microparticles (MPs), frequently involved in inflammation and thrombosis. CF enabled discovery of a unique pattern, involving both MPs and CPCs and generated a personalized signature of vascular health, the vascular health profile (VHP).
Levels of CPCs and MPs were measured with a broad panel of cell surface markers in a population with atherosclerosis and type 2 diabetes mellitus (DM) and age-similar Healthy controls (HC) using an unbiased computational approach, termed CF.
Circulating hematopoietic stem and progenitor cell (CHSPCAng) levels were detected at significantly lower concentrations in DM (P < 0.001), whereas levels of seven phenotypically distinct MPs were present at significantly higher concentrations in DM patients and one MP subset was present at significantly lower concentration in DM patients. Collectively, the combination of CHSPC(Ang) and MP levels was more informative than any one measure alone.
This work provides the basis for a personalized cytomic vascular health profile that may be useful for a variety of applications including drug development, clinical risk assessment and companion diagnostics.
目前尚无一种既经济又准确的血液检测方法可用于评估患者的心血管健康状况。本研究采用新型高维流式细胞术结合细胞计量指纹分析(CF),全面计数参与血管修复的促血管生成循环祖细胞(CPCs)和微颗粒(MPs)的差异表达亚群。CF 不仅能发现涉及 MPs 和 CPCs 的独特模式,还能生成个性化的血管健康特征,即血管健康特征谱(VHP)。
采用一种广泛的细胞表面标志物面板,使用一种称为 CF 的无偏计算方法,在患有动脉粥样硬化和 2 型糖尿病(DM)的人群以及年龄相似的健康对照(HC)中测量 CPCs 和 MPs 的水平。
DM 患者的循环造血干细胞和祖细胞(CHSPCAng)水平明显降低(P<0.001),而七种表型不同的 MPs 水平明显升高,一种 MP 亚群水平明显降低。总的来说,CHSPC(Ang)和 MP 水平的组合比任何单一指标都更具信息量。
本研究为个性化细胞血管健康特征谱提供了基础,该特征谱可能对包括药物开发、临床风险评估和伴随诊断在内的多种应用具有重要价值。