Al Mheid Ibhar, Hayek Salim S, Ko Yi-An, Akbik Faysal, Li Qunna, Ghasemzadeh Nima, Martin Greg S, Long Qi, Hammadah Muhammad, Maziar Zafari A, Vaccarino Viola, Waller Edmund K, Quyyumi Arshed A
From the Division of Cardiology, Emory Clinical Cardiovascular Research Institute, Emory-Georgia Tech, Predictive Health Institute, Atlanta, GA.
Circ Res. 2016 Sep 16;119(7):801-9. doi: 10.1161/CIRCRESAHA.116.308461. Epub 2016 Jul 19.
We investigated aging of human endogenous reparative capacity and aimed to clarify whether it is affected by presence of cardiovascular disease or its risk factors (RFs).
Circulating progenitor cell (PC) levels reflect endogenous regenerative potential. The effect on PC of healthy aging compared with aging with RFs or cardiovascular disease (CVD) is unknown. We examined whether exposure to RF and CVD leads to an accelerated decline in circulating PC with increasing age.
In 2792 adult subjects, 498 were free of RFs (smoking, diabetes mellitus, hypertension, or hyperlipidemia), 1036 subjects had 1 to 2 RF, and 1253 had ≥3 RFs or CVD. PC were enumerated by flow cytometry as CD45(med+) mononuclear cells expressing CD34 and subsets coexpressing CD133, CXCR4, and vascular endothelial growth factor receptor-2 epitopes. Younger age, male sex, and larger body size correlated with higher PC counts (P<0.01). After multivariable adjustment, both age and RF categories were independently associated with PC counts (P<0.05), with lower PC counts in older subjects and those with higher RF burden or CVD. PC counts remained unchanged with increasing age in healthy individuals. There were significant interactions between age and RF categories (P≤0.005), such that for younger subjects (<40 years), RFs were associated with increased PC counts, whereas for older subjects (>60 years), RFs and CVD were associated with lower PC counts.
Circulating PC levels do not decline with healthy aging; RF exposure at a younger age stimulates PC mobilization, whereas continued exposure is associated with lower PC levels in later life. Over the lifespan, exposure to RFs and CVD is associated with an initial stimulation and subsequent decline in circulating PC levels, which reflect endogenous regenerative capacity.
我们研究了人类内源性修复能力的老化情况，并旨在阐明其是否受心血管疾病或其危险因素（RFs）的影响。
循环祖细胞（PC）水平反映内源性再生潜力。与伴有RFs或心血管疾病（CVD）的老化相比，健康老化对PC的影响尚不清楚。我们研究了暴露于RFs和CVD是否会导致随着年龄增长循环PC加速下降。
在2792名成年受试者中，498人无RFs（吸烟、糖尿病、高血压或高脂血症），1036名受试者有1至2种RFs，1253名受试者有≥3种RFs或患有CVD。通过流式细胞术将PC计数为表达CD34的CD45（中等强度）单核细胞以及共表达CD133、CXCR4和血管内皮生长因子受体-2表位的亚群。年龄较小、男性以及体型较大与较高的PC计数相关（P<0.01）。经过多变量调整后，年龄和RF类别均与PC计数独立相关（P<0.05），老年受试者以及RF负担较高或患有CVD的受试者PC计数较低。健康个体的PC计数随年龄增长保持不变。年龄与RF类别之间存在显著交互作用（P≤0.005），即对于较年轻的受试者（<40岁），RFs与PC计数增加相关，而对于老年受试者（>60岁），RFs和CVD与较低的PC计数相关。
循环PC水平不会随着健康老化而下降；年轻时暴露于RFs会刺激PC动员，而持续暴露与晚年较低的PC水平相关。在整个生命周期中，暴露于RFs和CVD与循环PC水平的初始刺激及随后下降相关，循环PC水平反映内源性再生能力。
