Circulating CD34+ progenitor cells and risk of mortality in a population with coronary artery disease.
Circulating CD34+ progenitor cells and risk of mortality in a population with coronary artery disease.
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DOI：
10.1161/circresaha.116.304187
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发表时间：
2015-01-16
影响因子：
20.1
通讯作者：
Quyyumi AA
中科院分区：
文献类型：
--
作者：
Patel RS;Li Q;Ghasemzadeh N;Eapen DJ;Moss LD;Janjua AU;Manocha P;Kassem HA;Veledar E;Samady H;Taylor WR;Zafari AM;Sperling L;Vaccarino V;Waller EK;Quyyumi AA
循环祖细胞（PC）数量和活性低可能反映了内在再生/修复潜力受损，但仍不确定这是否会导致更糟糕的预后。调查低 PC 数量是否与心血管高风险人群较高的死亡风险相关。在不同的时间段内将接受冠状动脉造影的患者分为两个队列（1，n = 502 和 2，n = 403）。通过流式细胞术将 PC 计数为表达 CD34 的 CD45med+ 血液单核细胞，并对共表达 CD133、VEGFR2 和 CXCR4 的子集进行额外定量。各个亚群的 CD34+ 细胞的变异系数分别为 2.9% 和 4.8%、21.6% 和 6.5%。每个队列的主要终点全因死亡分别平均随访 2.7 年和 1.2 年。在队列 1 中，CD34+ 和 CD34+/CD133+ 细胞计数与死亡风险之间存在负相关（分别为 β=-0.92，p=0.043 和 β=-1.64，p=0.019），这在队列 2 中得到证实（分别为 β=-1.25，p=0.020 和 β=-1.81，p=0.015）。合并队列 (n=905) 中的协变量调整 HR 分别为 3.54 (1.67-7.50) 和 2.46 (1.18-5.13)。 CD34+/CD133+ 细胞计数改进的风险预测指标超出了标准风险因素。循环 PC 计数（主要为 CD34+ 单核细胞或其表达 CD133 的子集）减少与冠状动脉疾病患者的死亡风险相关，表明内源性再生能力受损与死亡率增加相关。这些发现对细胞疗法的生物学理解、风险预测和细胞选择具有重要意义。
Low circulating progenitor cell (PC) numbers and activity may reflect impaired intrinsic regenerative/reparative potential, but it remains uncertain whether this translates into a worse prognosis. To investigate whether low numbers of PCs associate with a greater risk of mortality in a population at high cardiovascular risk. Patients undergoing coronary angiography were recruited into two cohorts (1, n=502 and 2, n=403) over separate time periods. PCs were enumerated by flow cytometry as CD45med+ blood mononuclear cells expressing CD34, with additional quantification of subsets co-expressing CD133, VEGFR2 and CXCR4. Coefficient of variation for CD34 cells was 2.9% and 4.8%, 21.6% and 6.5% for the respective subsets. Each cohort was followed for a mean of 2.7 and 1.2 years, respectively, for the primary endpoint of all-cause death. There was an inverse association between CD34+ and CD34+/CD133+ cell counts and risk of death in Cohort 1 (β=−0.92, p=0.043 and β=−1.64, p=0.019, respectively) that was confirmed in Cohort 2 (β=−1.25, p=0.020 and β=−1.81, p=0.015, respectively). Covariate adjusted HRs in the pooled cohort (n=905) were 3.54 (1.67-7.50) and 2.46 (1.18-5.13), respectively. CD34+/CD133+ cell counts improved risk prediction metrics beyond standard risk factors. Reduced circulating PC counts, identified primarily as CD34+ mononuclear cells or its subset expressing CD133 are associated with risk of death in individuals with coronary artery disease, suggesting that impaired endogenous regenerative capacity is associated with increased mortality. These findings have implications for biological understanding, risk prediction and cell selection for cell based therapies.