High-density lipoproteins enhance progenitor-mediated endothelium repair in mice.
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.