Aging, progenitor cell exhaustion, and atherosclerosis

Background - Atherosclerosis is largely attributed to chronic vascular injury, as occurs with excess cholesterol; however, the effect of concomitant vascular aging remains unexplained. We hypothesize that the effect of time in atherosclerosis progression is related to obsolescence of endogenous progenitor cells that normally repair and rejuvenate the arteries. Methods and Results - Here we show that chronic treatment with bone marrow-derived progenitor cells from young nonatherosclerotic ApoE^-/- mice prevents atherosclerosis progression in ApoE^-/- recipients despite persistent hypercholesterolemia. In contrast, treatment with bone marrow cells from older ApoE^-/- mice with atherosclerosis is much less effective. Cells with vascular progenitor potential are decreased in the bone marrow of aging ApoE^-/- mice, but cells injected from donor mice engraft on recipient arteries in areas at risk for atherosclerotic injury. Conclusions - Our data indicate that progressive progenitor cell deficits may contribute to the development of atherosclerosis.