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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1144.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

High-Density Lipoproteins Enhance Progenitor-Mediated Endothelium Repair in Mice

Colin Tso; Gary Martinic; Wen-Hua Fan; Campbell Rogers; Kerry-Anne Rye; Philip J. Barter

From the Heart Research Institute (C.T., G.M., K.-A.R., P.J.B.), Sydney, Australia; Harvard-MIT Division of Health Sciences and Technology (W.-H.F., C.R.), Massachusetts Institute of Technology, Boston; Cardiovascular Division (C.R.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; Department of Medicine (K.-A.R., P.J.B.), University of Sydney, Australia; and Department of Medicine (K.-A.R.), University of Melbourne, Australia.

Correspondence to Philip J. Barter, Heart Research Institute, 145 Missenden Rd, Camperdown, Sydney, NSW 2050, Australia. E-mail p.barter{at}hri.org.au

Objective— We quantified endothelial progenitor cell (EPC) engraftment into the endothelial layer as an index of progenitor-mediated endothelial repair. Studies were conducted in C57BL/6J and in apolipoprotein E–deficient (apoE^–/–) mice. We also investigated the possibility that high-density lipoproteins (HDL) may promote progenitor-mediated endothelial repair.

Methods and Results— Thoracic aortic sections from C57BL/6J and apoE^–/– mice were analyzed for evidence of progenitor-derived endothelium as determined by the number of stem cell antigen-1–positive (Sca-1+) cells in the endothelial layer. EPCs (Sca-1+ cells) were significantly increased after endothelial damage induced by lipopolysaccharide (LPS) administration in C57BL/6J mice. The number of EPCs was greater in the aortic endothelium of untreated apoE^–/– than in untreated C57BL/6J mice and was similar to the number observed in LPS-treated C57BL/6J mice. The number of EPCs in the aortic endothelium of apoE^–/– mice more than doubled after intravenous infusion of reconstituted HDL.

Conclusions— EPCs are recruited into the aortic endothelial layer of mice in response to an inflammatory insult. EPCs are also increased in the aortic endothelium of untreated apoE^–/– mice. The observation that number is further increased in apoE^–/– mice after injection of HDL suggests a role for HDL in promoting progenitor-mediated endothelial repair.

The number of endothelial progenitor cells (EPCs) in the aortic endothelium of mice is increased in response to vascular injury, consistent with a role of EPCs in endothelial repair. In apoE^–/– mice, the number is further increased after injection of HDL, suggesting a role for HDL in promoting progenitor-mediated endothelial repair.

Key Words: endothelial progenitor cells • high-density lipoproteins • mouse • endothelial damage

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