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. 2016 Sep 16;119(7):801-9.
doi: 10.1161/CIRCRESAHA.116.308461. Epub 2016 Jul 19.

Age and Human Regenerative Capacity Impact of Cardiovascular Risk Factors

Ibhar Al Mheid  1 , Salim S Hayek  1 , Yi-An Ko  1 , Faysal Akbik  1 , Qunna Li  1 , Nima Ghasemzadeh  1 , Greg S Martin  1 , Qi Long  1 , Muhammad Hammadah  1 , A Maziar Zafari  1 , Viola Vaccarino  1 , Edmund K Waller  1 , Arshed A Quyyumi  2
Affiliations

Age and Human Regenerative Capacity Impact of Cardiovascular Risk Factors

Ibhar Al Mheid et al. Circ Res. .

Abstract

Rationale: 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).

Objective: 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.

Methods and results: 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.

Conclusions: 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.

Keywords: aging; cardiovascular risk factors; progenitor cells.

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Figures

Figure 1
Figure 1. The relationship between age and PC
r: correlation coefficient and associated p-value. Fit lines are solid and dashed lines represent the 95% confidence intervals. N=2792.
Figure 2
Figure 2. Cardiovascular risk factor burden and PC counts in younger vs. older subjects
Effects of RF burden on PC counts in younger vs. older subjects. Estimated mean ± standard error PC counts with increasing cardiovascular risk factor burden in subjects > 55 years of age (N=1592) compared to those ≤ 55 years old (N=1200). Estimates were obtained by setting gender as female, BMI=28 kg/m2, and no statin use. P-values are for comparisons among three risk groups.
Figure 3
Figure 3. Effects of increasing risk factor burden on age-related decline of PC counts
Decreases in PC counts with increasing age among the three risk groups. P-values for the age effect on PC counts are shown for each risk group. All analyses were adjusted for gender, BMI, and statin use. *p ≤ 0.05 compared with no RF group, **p < 0.0001 compared with no RF group. RF: Risk factors
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