• 1
    Botusan IR, Sunkari VG, Savu O et al. Stabilization of HIF-1alpha is critical to improve wound healing in diabetic mice. Proc Natl Acad Sci USA 2008;105:1942619431.
  • 2
    Thangarajah H, Vial IN, Grogan RH et al. HIF-1alpha dysfunction in diabetes. Cell Cycle 2010;9:7579.
  • 3
    Segers VF, Lee RT. Stem-cell therapy for cardiac disease. Nature 2008;451:937942.
  • 4
    Aranguren XL, Verfaillie CM, Luttun A. Emerging hurdles in stem cell therapy for peripheral vascular disease. J Mol Med 2009;87:316.
  • 5
    Jin P, Zhang X, Wu Y et al. Streptozotocin-induced diabetic rat-derived bone marrow mesenchymal stem cells have impaired abilities in proliferation, paracrine, antiapoptosis, and myogenic differentiation. Transplant Proc 2010;42:27452752.
  • 6
    Mees B, Recalde A, Loinard C et al. Endothelial nitric oxide synthase overexpression restores the efficiency of bone marrow mononuclear cell-based therapy. Am J Pathol 2011;178:5560.
  • 7
    Ebrahimian TG, Heymes C, You D et al. NADPH oxidase-derived overproduction of reactive oxygen species impairs postischemic neovascularization in mice with type 1 diabetes. Am J Pathol 2006;169:719728.
  • 8
    Bosch-Marce M, Okuyama H, Wesley JB et al. Effects of aging and hypoxia-inducible factor-1 activity on angiogenic cell mobilization and recovery of perfusion after limb ischemia. Circ Res 2007;101:13101318.
  • 9
    Loinard C, Ginouves A, Vilar J et al. Inhibition of prolyl hydroxylase domain proteins promotes therapeutic revascularization. Circulation 2009;120:5059.
  • 10
    Takeda Y, Costa S, Delamarre E et al. Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis. Nature 2011;479:122126.
  • 11
    Bento CF, Pereira P. Regulation of hypoxia-inducible factor 1 and the loss of the cellular response to hypoxia in diabetes. Diabetologia 2011;54:19461956.
  • 12
    Sarkar K, Fox-Talbot K, Steenbergen C et al. Adenoviral transfer of HIF-1alpha enhances vascular responses to critical limb ischemia in diabetic mice. Proc Natl Acad Sci USA 2009;106:1876918774.
  • 13
    Warnecke C, Griethe W, Weidemann A et al. Activation of the hypoxia-inducible factor-pathway and stimulation of angiogenesis by application of prolyl hydroxylase inhibitors. FASEB J 2003;17:11861188.
  • 14
    Nangaku M, Izuhara Y, Takizawa S et al. A novel class of prolyl hydroxylase inhibitors induces angiogenesis and exerts organ protection against ischemia. Arterioscler Thromb Vasc Biol 2007;27:25482554.
  • 15
    Rey S, Lee K, Wang CJ et al. Synergistic effect of HIF-1alpha gene therapy and HIF-1-activated bone marrow-derived angiogenic cells in a mouse model of limb ischemia. Proc Natl Acad Sci USA 2009;106:2039920404.
  • 16
    Wei L, Fraser JL, Lu ZY et al. Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and neurogenesis after cerebral ischemia in rats. Neurobiol Dis 2012;46:635645.
  • 17
    Leroux L, Descamps B, Tojais NF et al. Hypoxia preconditioned mesenchymal stem cells improve vascular and skeletal muscle fiber regeneration after ischemia through a Wnt4-dependent pathway. Mol Ther 2010;18:15451552.
  • 18
    Hu X, Yu SP, Fraser JL et al. Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. J Thorac Cardiovasc Surg 2008;135:799808.
  • 19
    Tang YL, Zhu W, Cheng M et al. Hypoxic preconditioning enhances the benefit of cardiac progenitor cell therapy for treatment of myocardial infarction by inducing CXCR4 expression. Circ Res 2009;104:12091216.
  • 20
    Huang M, Nguyen P, Jia F et al. Double knockdown of prolyl hydroxylase and factor-inhibiting hypoxia-inducible factor with nonviral minicircle gene therapy enhances stem cell mobilization and angiogenesis after myocardial infarction. Circulation 2011;124:S4654.
  • 21
    Smadja DM, Duong-van-Huyen JP, Dal Cortivo L et al. Early endothelial progenitor cells in bone marrow are a biomarker of cell therapy success in patients with critical limb ischemia. Cytotherapy 2012;14:232239.
  • 22
    Tateishi-Yuyama E, Matsubara H, Murohara T et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: A pilot study and a randomised controlled trial. Lancet 2002;360:427435.
  • 23
    Duong Van Huyen JP, Smadja DM, Bruneval P et al. Bone marrow-derived mononuclear cell therapy induces distal angiogenesis after local injection in critical leg ischemia. Mod Pathol 2008;21:837846.
  • 24
    Smadja DM, d'Audigier C, Guerin CL et al. Angiogenic potential of BM MSCs derived from patients with critical leg ischemia. Bone Marrow Transplant 2012;47:9971000.
  • 25
    Foubert P, Silvestre JS, Souttou B et al. PSGL-1-mediated activation of EphB4 increases the proangiogenic potential of endothelial progenitor cells. J Clin Invest 2007;117:15271537.
  • 26
    Tamarat R, Silvestre JS, Huijberts M et al. Blockade of advanced glycation end-product formation restores ischemia-induced angiogenesis in diabetic mice. Proc Natl Acad Sci USA 2003;100:85558560.
  • 27
    Broqueres-You D, Lere-Dean C, Merkulova-Rainon T et al. Ephrin-B2-activated peripheral blood mononuclear cells from diabetic patients restore diabetes-induced impairment of postischemic neovascularization. Diabetes 2012;61:26212632.
  • 28
    Smadja DM, Bieche I, Silvestre JS et al. Bone morphogenetic proteins 2 and 4 are selectively expressed by late outgrowth endothelial progenitor cells and promote neoangiogenesis. Arterioscler Thromb Vasc Biol 2008;28:21372143.
  • 29
    Smadja DM, d'Audigier C, Bieche I et al. Thrombospondin-1 is a plasmatic marker of peripheral arterial disease that modulates endothelial progenitor cell angiogenic properties. Arterioscler Thromb Vasc Biol 2011;31:551559.
  • 30
    Berra E, Benizri E, Ginouves A et al. HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. EMBO J 2003;22:40824090.
  • 31
    Palomaki S, Pietila M, Laitinen S et al. HIF-1alpha is upregulated in human mesenchymal stem cells. Stem Cells 2013 Jun 6. doi: 10.1002/stem.1435.
  • 32
    Kinnaird T, Stabile E, Burnett MS et al. Bone-marrow-derived cells for enhancing collateral development: Mechanisms, animal data, and initial clinical experiences. Circ Res 2004;95:354363.
  • 33
    Timmers L, Lim SK, Arslan F et al. Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. Stem Cell Res 2007;1:129137.
  • 34
    Forsythe JA, Jiang BH, Iyer NV et al. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 1996;16:46044613.
  • 35
    Toma C, Pittenger MF, Cahill KS et al. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 2002;105:9398.
  • 36
    Rey S, Luo W, Shimoda LA et al. Metabolic reprogramming by HIF-1 promotes the survival of bone marrow-derived angiogenic cells in ischemic tissue. Blood 2011;117:49884998.
  • 37
    Rosova I, Dao M, Capoccia B et al. Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem Cells 2008;26:21732182.
  • 38
    Ito WD, Arras M, Winkler B et al. Monocyte chemotactic protein-1 increases collateral and peripheral conductance after femoral artery occlusion. Circ Res 1997;80:829837.
  • 39
    Cochain C, Rodero MP, Vilar J et al. Regulation of monocyte subset systemic levels by distinct chemokine receptors controls post-ischaemic neovascularization. Cardiovasc Res 2010;88:186195.
  • 40
    Swirski FK, Nahrendorf M, Etzrodt M et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 2009;325:612616.
  • 41
    Jin DK, Shido K, Kopp HG et al. Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes. Nat Med 2006;12:557567.
  • 42
    Yeligar SM, Machida K, Tsukamoto H et al. Ethanol augments RANTES/CCL5 expression in rat liver sinusoidal endothelial cells and human endothelial cells via activation of NF-kappa B, HIF-1 alpha, and AP-1. J Immunol 2009;183:59645976.
  • 43
    Jiang X, Khan MA, Tian W et al. Adenovirus-mediated HIF-1alpha gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection. J Clin Invest 2011;121:23362349.
  • 44
    Farha S, Asosingh K, Xu W et al. Hypoxia-inducible factors in human pulmonary arterial hypertension: A link to the intrinsic myeloid abnormalities. Blood 2011;117:34853493.
  • 45
    Asosingh K, Farha S, Lichtin A et al. Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension. Blood 2012;120:12181227.
  • 46
    Ho TK, Rajkumar V, Ponticos M et al. Increased endogenous angiogenic response and hypoxia-inducible factor-1alpha in human critical limb ischemia. J Vasc Surg 2006;43:125133.
  • 47
    Ginouves A, Ilc K, Macias N et al. PHDs overactivation during chronic hypoxia “desensitizes” Hifalpha and protects cells from necrosis. Proc Natl Acad Sci USA 2008;105:47454750.
  • 48
    Catrina SB, Okamoto K, Pereira T et al. Hyperglycemia regulates hypoxia-inducible factor-1alpha protein stability and function. Diabetes 2004;53:32263232.
  • 49
    Ceradini DJ, Yao D, Grogan RH et al. Decreasing intracellular superoxide corrects defective ischemia-induced new vessel formation in diabetic mice. J Biol Chem 2008;283:1093010938.
  • 50
    Bento CF, Marques F, Fernandes R et al. Methylglyoxal alters the function and stability of critical components of the protein quality control. PLoS One 2010;5:e13007.
  • 51
    Basic VT, Tadele E, Elmabsout AA et al. Exposure to cigarette smoke induces overexpression of von Hippel-Lindau tumor suppressor in mouse skeletal muscle. Am J Physiol Lung Cell Mol Physiol 2012;303:L519527.
  • 52
    Michaud SE, Menard C, Guy LG et al. Inhibition of hypoxia-induced angiogenesis by cigarette smoke exposure: Impairment of the HIF-1alpha/VEGF pathway. FASEB J 2003;17:11501152.
  • 53
    Melero-Martin JM, De Obaldia ME, Kang SY et al. Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ Res 2008;103:194202.
  • 54
    Deuse T, Peter C, Fedak PW et al. Hepatocyte growth factor or vascular endothelial growth factor gene transfer maximizes mesenchymal stem cell-based myocardial salvage after acute myocardial infarction. Circulation 2009;120:S247254.
  • 55
    Li H, Zuo S, He Z et al. Paracrine factors released by GATA-4 overexpressed mesenchymal stem cells increase angiogenesis and cell survival. Am J Physiol Heart Circ Physiol 2010;299:H17721781.
  • 56
    Busletta C, Novo E, Valfre Di Bonzo L et al. Dissection of the biphasic nature of hypoxia-induced motogenic action in bone marrow-derived human mesenchymal stem cells. Stem Cells 2011;29:952963.
  • 57
    Ziegelhoeffer T, Fernandez B, Kostin S et al. Bone marrow-derived cells do not incorporate into the adult growing vasculature. Circ Res 2004;94:230238.
  • 58
    Cho HJ, Lee N, Lee JY et al. Role of host tissues for sustained humoral effects after endothelial progenitor cell transplantation into the ischemic heart. J Exp Med 2007;204:32573269.
  • 59
    Ryu JC, Davidson BP, Xie A et al. Molecular imaging of the paracrine proangiogenic effects of progenitor cell therapy in limb ischemia. Circulation 2013;127:710719.
  • 60
    Tepper OM, Galiano RD, Capla JM et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 2002;106:27812786.
  • 61
    Fadini GP, Miorin M, Facco M et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol 2005;45:14491457.
  • 62
    Sasso FC, Torella D, Carbonara O et al. Increased vascular endothelial growth factor expression but impaired vascular endothelial growth factor receptor signaling in the myocardium of type 2 diabetic patients with chronic coronary heart disease. J Am Coll Cardiol 2005;46:827834.
  • 63
    Caporali A, Pani E, Horrevoets AJ et al. Neurotrophin p75 receptor (p75NTR) promotes endothelial cell apoptosis and inhibits angiogenesis: Implications for diabetes-induced impaired neovascularization in ischemic limb muscles. Circ Res 2008;103:e1526.
  • 64
    Sodha NR, Clements RT, Boodhwani M et al. Endostatin and angiostatin are increased in diabetic patients with coronary artery disease and associated with impaired coronary collateral formation. Am J Physiol Heart Circ Physiol 2009;296:H428434.
  • 65
    Waltenberger J, Lange J, Kranz A. Vascular endothelial growth factor-A-induced chemotaxis of monocytes is attenuated in patients with diabetes mellitus: A potential predictor for the individual capacity to develop collaterals. Circulation 2000;102:185190.
  • 66
    Caporali A, Meloni M, Vollenkle C et al. Deregulation of microRNA-503 contributes to diabetes mellitus-induced impairment of endothelial function and reparative angiogenesis after limb ischemia. Circulation 2011;123:282291.
  • 67
    Fraisl P, Aragones J, Carmeliet P. Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease. Nat Rev Drug Discov 2009;8:139152.