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.

[1]  A. Lafont,et al.  Isolation of “Side Population” Progenitor Cells From Healthy Arteries of Adult Mice , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[2]  Qingbo Xu,et al.  Abundant progenitor cells in the adventitia contribute to atherosclerosis of vein grafts in ApoE-deficient mice. , 2004, The Journal of clinical investigation.

[3]  D. Bonnet,et al.  Multiparameter analysis of murine bone marrow side population cells. , 2004, Blood.

[4]  H. Kubo,et al.  Bone Marrow-Derived Progenitor Cells Are Important for Lung Repair after Lipopolysaccharide-Induced Lung Injury 1 , 2004, The Journal of Immunology.

[5]  T. Imanishi,et al.  Oxidized low‐density lipoprotein inhibits vascular endothelial growth factor‐induced endothelial progenitor cell differentiation , 2003, Clinical and experimental pharmacology & physiology.

[6]  M. Reilly,et al.  Overexpression of Apolipoprotein A-I Promotes Reverse Transport of Cholesterol From Macrophages to Feces In Vivo , 2003, Circulation.

[7]  T. Rabelink,et al.  Bone-marrow-derived cells contribute to glomerular endothelial repair in experimental glomerulonephritis. , 2003, The American journal of pathology.

[8]  D. Kotton,et al.  Stem cell antigen-1 expression in the pulmonary vascular endothelium. , 2003, American journal of physiology. Lung cellular and molecular physiology.

[9]  J. Aubin,et al.  Mesenchymal progenitor self-renewal deficiency leads to age-dependent osteoporosis in Sca-1/Ly-6A null mice , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Elaine Dzierzak,et al.  The Ly‐6A (Sca‐1) GFP Transgene is Expressed in all Adult Mouse Hematopoietic Stem Cells , 2002, Stem cells.

[11]  M. Endres,et al.  Bone Marrow–Derived Progenitor Cells Modulate Vascular Reendothelialization and Neointimal Formation: Effect of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibition , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[12]  J. Isner,et al.  Statin Therapy Accelerates Reendothelialization: A Novel Effect Involving Mobilization and Incorporation of Bone Marrow-Derived Endothelial Progenitor Cells , 2002, Circulation.

[13]  V. Edgerton,et al.  Identification of myogenic-endothelial progenitor cells in the interstitial spaces of skeletal muscle , 2002, The Journal of cell biology.

[14]  S. Fichtlscherer,et al.  Number and Migratory Activity of Circulating Endothelial Progenitor Cells Inversely Correlate With Risk Factors for Coronary Artery Disease , 2001, Circulation research.

[15]  E. Topol,et al.  Tissue factor, the emerging link between inflammation, thrombosis, and vascular remodeling. , 2001, Circulation research.

[16]  Xin Wang,et al.  Purified hematopoietic stem cells can differentiate into hepatocytes in vivo , 2000, Nature Medicine.

[17]  S. Rafii,et al.  Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. , 2000, Blood.

[18]  M. Cybulsky,et al.  Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. , 1999, Circulation research.

[19]  Haruchika Masuda,et al.  Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization , 1999, Nature Medicine.

[20]  R. Ross,et al.  Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[21]  M. Ballmaier,et al.  Downregulation of c-kit expression in human endothelial cells by inflammatory stimuli. , 1997, Blood.

[22]  Takayuki Asahara,et al.  Isolation of Putative Progenitor Endothelial Cells for Angiogenesis , 1997, Science.

[23]  V. Ord,et al.  ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis. Demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehyde-lysine in serum. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[24]  T. Quinn,et al.  Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[25]  P. Barter,et al.  Changes in the size of reconstituted high density lipoproteins during incubation with cholesteryl ester transfer protein: the role of apolipoproteins. , 1992, Journal of lipid research.

[26]  T. Malek,et al.  Regulation of B lymphocyte responses to IL-4 and IFN-gamma by activation through Ly-6A/E molecules. , 1990, Journal of immunology.

[27]  I. Weissman,et al.  Mouse hematopoietic stem-cell antigen Sca-1 is a member of the Ly-6 antigen family. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[28]  T. Malek,et al.  Tumor necrosis factor synergistically acts with IFN-gamma to regulate Ly-6A/E expression in T lymphocytes, thymocytes and bone marrow cells. , 1989, Journal of immunology.

[29]  I. Weissman,et al.  Purification and characterization of mouse hematopoietic stem cells. , 1988, Science.

[30]  P. Wilson,et al.  Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. , 1986, JAMA.

[31]  H. Ochs,et al.  An endothelial cell surface factor(s) induced in vitro by lipopolysaccharide, interleukin 1, and tumor necrosis factor-alpha increases neutrophil adherence by a CDw18-dependent mechanism. , 1986, Journal of immunology.

[32]  R. Schleimer,et al.  Cultured human vascular endothelial cells acquire adhesiveness for neutrophils after stimulation with interleukin 1, endotoxin, and tumor-promoting phorbol diesters. , 1986, Journal of immunology.

[33]  M. Wong,et al.  Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells. , 2004, Blood.

[34]  M. Goodell,et al.  Distinct progenitor populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration. , 2003, The Journal of clinical investigation.

[35]  R. Hebbel,et al.  Origins of circulating endothelial cells and endothelial outgrowth from blood. , 2000, The Journal of clinical investigation.

[36]  S. Schwartz,et al.  Endothelial injury and regeneration. IV. Endotoxin: a nondenuding injury to aortic endothelium. , 1983, Laboratory investigation; a journal of technical methods and pathology.

[37]  R. Ma,et al.  Endothelial injury and regeneration. IV. Endotoxin: a nondenuding injury to aortic endothelium. , 1983 .