Patel Riyaz S, Li Qunna, Ghasemzadeh Nima, Eapen Danny J, Moss Lauren D, Janjua A Umair, Manocha Pankaj, Kassem Hatem Al, Veledar Emir, Samady Habib, Taylor W Robert, Zafari A Maziar, Sperling Laurence, Vaccarino Viola, Waller Edmund K, Quyyumi Arshed A
Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Institute of Cardiovascular Sciences, University College London, London, UK.
Circ Res. 2015 Jan 16;116(2):289-297. doi: 10.1161/CIRCRESAHA.116.304187. Epub 2014 Oct 16.
Low circulating progenitor cell 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 progenitor cells associate with a greater risk of mortality in a population at high cardiovascular risk.
Patients undergoing coronary angiography were recruited into 2 cohorts (1, n=502 and 2, n=403) over separate time periods. Progenitor cells were enumerated by flow cytometry as CD45(med+) blood mononuclear cells expressing CD34, with additional quantification of subsets coexpressing CD133, vascular endothelial growth factor receptor 2, and chemokine (C-X-C motif) receptor 4. 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 end point 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 hazard ratios 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 progenitor cell 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.
循环祖细胞数量和活性较低可能反映出内在再生/修复潜能受损，但这是否会转化为更差的预后仍不确定。
研究在心血管疾病高风险人群中，祖细胞数量少是否与更高的死亡风险相关。
在不同时间段，将接受冠状动脉造影的患者纳入两个队列（队列1，n = 502；队列2，n = 403）。通过流式细胞术将祖细胞计数为表达CD34的CD45（中等强度）血液单核细胞，并对共表达CD133、血管内皮生长因子受体2和趋化因子（C-X-C基序）受体4的亚群进行额外定量。CD34细胞的变异系数分别为2.9%和4.8%，各亚群分别为21.6%和6.5%。每个队列分别随访平均2.7年和1.2年，以全因死亡作为主要终点。队列1中，CD34(+)和CD34(+)/CD133(+)细胞计数与死亡风险呈负相关（β分别为-0.92，P = 0.043和β为-1.64，P = 0.019），队列2中也得到证实（β分别为-1.25，P = 0.020和β为-1.81，P = 0.015）。合并队列（n = 905）中经协变量调整的风险比分别为3.54（1.67 - 7.50）和2.46（1.18 - 5.13）。CD34(+)/CD133(+)细胞计数改善了超出标准风险因素的风险预测指标。
循环祖细胞计数减少，主要表现为CD34(+)单核细胞或其表达CD133的亚群减少，与冠心病患者的死亡风险相关，提示内源性再生能力受损与死亡率增加有关。这些发现对生物学理解、风险预测以及基于细胞治疗的细胞选择具有重要意义。
