Circulation. 2003;108:457-463
Published online before print July 14, 2003, doi: 10.1161/01.CIR.0000082924.75945.48
Published online before print July 14, 2003, doi: 10.1161/01.CIR.0000082924.75945.48
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(Circulation. 2003;108:457.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Aging, Progenitor Cell Exhaustion, and Atherosclerosis
From the Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC.
Correspondence to Pascal J. Goldschmidt-Clermont, MD, and Doris A. Taylor, PhD, Department of Medicine, Duke University Medical Center, Box 3845, Durham, NC 27710. E-mail pascal.goldschmidt{at}duke.edu or dataylor@duke.edu
Received April 22, 2003; de novo received May 30, 2003; accepted June 11, 2003.
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.
Key Words: aging • atherosclerosis • stem cells
Related Article:
Circulation 2003 108: 378-379.
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T. Kinnaird, E. Stabile, M. S. Burnett, and S. E. Epstein Bone Marrow-Derived Cells for Enhancing Collateral Development: Mechanisms, Animal Data, and Initial Clinical Experiences Circ. Res., August 20, 2004; 95(4): 354 - 363. [Abstract] [Full Text] [PDF]
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B. Hibbert, Y.-X. Chen, and E. R. O'Brien c-kit-Immunopositive vascular progenitor cells populate human coronary in-stent restenosis but not primary atherosclerotic lesions Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H518 - H524. [Abstract] [Full Text] [PDF]
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E. G. Lakatta and S. Schulman Age-associated cardiovascular changes are the substrate for poor prognosis with myocardial infarction J. Am. Coll. Cardiol., July 7, 2004; 44(1): 35 - 37. [Full Text] [PDF]
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J.-H. Choi, K. L. Kim, W. Huh, B. Kim, J. Byun, W. Suh, J. Sung, E.-S. Jeon, H.-Y. Oh, and D.-K. Kim Decreased Number and Impaired Angiogenic Function of Endothelial Progenitor Cells in Patients With Chronic Renal Failure Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1246 - 1252. [Abstract] [Full Text] [PDF]
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J. Rehman, J. Li, L. Parvathaneni, G. Karlsson, V. R. Panchal, C. J. Temm, J. Mahenthiran, and K. L. March Exercise acutely increases circulating endothelial progenitor cells and monocyte-/macrophage-derived angiogenic cells J. Am. Coll. Cardiol., June 16, 2004; 43(12): 2314 - 2318. [Abstract] [Full Text] [PDF]
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S. E. Epstein, E. Stabile, T. Kinnaird, C. W. Lee, L. Clavijo, and M. S. Burnett Janus Phenomenon: The Interrelated Tradeoffs Inherent in Therapies Designed to Enhance Collateral Formation and Those Designed to Inhibit Atherogenesis Circulation, June 15, 2004; 109(23): 2826 - 2831. [Full Text] [PDF]
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 J. George, E. Goldstein, S. Abashidze, V. Deutsch, H. Shmilovich, A. Finkelstein, I. Herz, H. Miller, and G. Keren Circulating endothelial progenitor cells in patients with unstable angina: association with systemic inflammation Eur. Heart J., June 2, 2004; 25(12): 1003 - 1008. [Abstract] [Full Text] [PDF]
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C. Heeschen, R. Lehmann, J. Honold, B. Assmus, A. Aicher, D. H. Walter, H. Martin, A. M. Zeiher, and S. Dimmeler Profoundly Reduced Neovascularization Capacity of Bone Marrow Mononuclear Cells Derived From Patients With Chronic Ischemic Heart Disease Circulation, April 6, 2004; 109(13): 1615 - 1622. [Abstract] [Full Text] [PDF]
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M. Heil, T. Ziegelhoeffer, B. Mees, and W. Schaper A Different Outlook on the Role of Bone Marrow Stem Cells in Vascular Growth: Bone Marrow Delivers Software not Hardware Circ. Res., March 19, 2004; 94(5): 573 - 574. [Full Text] [PDF]
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M. C. Capogrossi Cardiac Stem Cells Fail With Aging: A New Mechanism for the Age-Dependent Decline in Cardiac Function Circ. Res., March 5, 2004; 94(4): 411 - 413. [Full Text] [PDF]
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J. George, I. Herz, E. Goldstein, S. Abashidze, V. Deutch, A. Finkelstein, Y. Michowitz, H. Miller, and G. Keren Number and Adhesive Properties of Circulating Endothelial Progenitor Cells in Patients With In-Stent Restenosis Arterioscler Thromb Vasc Biol, December 1, 2003; 23(12): e57 - e60. [Abstract] [Full Text] [PDF]
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 P. J. Goldschmidt-Clermont and E. D. Peterson On the Memory of a Chronic Illness Sci. Aging Knowl. Environ., November 12, 2003; 2003(45): re8 - 8. [Abstract] [Full Text] [PDF]
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Q. Xu, Z. Zhang, F. Davison, and Y. Hu Circulating Progenitor Cells Regenerate Endothelium of Vein Graft Atherosclerosis, Which Is Diminished in ApoE-Deficient Mice Circ. Res., October 17, 2003; 93 (8): e76 - e86. [Abstract] [Full Text] [PDF]
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P. Libby Bone Marrow: A Fountain of Vascular Youth? Circulation, July 29, 2003; 108(4): 378 - 379. [Full Text] [PDF]
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