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.


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.
Rauscher
Frederick M
FM
Division of Cardiology, Department of Medicine, Duke University Medical Center, Box 3845, Durham, NC 27710, USA.
Goldschmidt-Clermont
Pascal J
PJ
Davis
Bryce H
BH
Wang
Tao
T
Gregg
David
D
Ramaswami
Priya
P
Pippen
Anne M
AM
Annex
Brian H
BH
Dong
Chunming
C
Taylor
Doris A
DA
D000367:Age Factors; D000375:Aging / Q000235:genetics; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D002452:Cell Count; D004041:Dietary Fats; D018450:Disease Progression; D005434:Flow Cytometry; D006085:Graft Survival; D006937:Hypercholesterolemia / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D012307:Risk Factors; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology
D001057:Apolipoproteins E; D004041:Dietary Fats; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017493:Leukocyte Common Antigens