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Submitted on July 10, 2005
Accepted on February 23, 2006
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.
* To whom correspondence should be addressed. 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 (HDLs) 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 HDLs suggests a role for HDLs in promoting progenitor-mediated endothelial repair.
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