Abstract 16787: Impact of Aging on Progenitor Cell Homing for Angiogenesis
Reduced numbers and activity of circulating progenitor stem cells are associated with aging and have been linked with coronary artery disease. Chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 mediate bone marrow cell mobilization, tissue homing and engraftment. We recently reported that calcium regulates CXCR4 expression in combination with SDF-1. We assessed the hypothesis that defective CXCR4 expression develops with aging and disease, which results in less progenitor cell homing to vascular lesion site and inefficient repair. CXCR4 expression and its function were compared between bone marrow cells of aged ApoE null mice (ApoE-/-) that had been fed with a high-fat, high-cholesterol diet for 6-months and 6-week old young ApoE-/- mice. We found that CXCR4 surface expression is age-dependent. Age and atherosclerosis correlated with significantly lower surface expression of CXCR4 that was less inducible by calcium. The impaired calcium response was associated with defective calcium influx and was partially recovered by treatment with the calcium ionophore ionomycin. The aged ApoE-/- mice fed high fat for 6-months had similar characteristics as the 24-month old wild type mice in defective CXCR4 expression and SDF-1 regulation. Cells from aged, atherogenic ApoE-/- mice also displayed defective homing to SDF-1 and the animals had lower serum and bone marrow levels of SDF-1. We conclude that during the evolution of atherosclerosis in ApoE-/- mice there is a progressively reduction of bone marrow cell CXCR4 expression and function, and reduced serum and bone marrow levels of SDF-1. These changes mute the homing capability of bone marrow cells and may contribute to the progression of atherosclerosis in this model.
- © 2011 by American Heart Association, Inc.