Myocardial therapeutic angiogenesis: a review of the state of development and future obstacles

References

• Lloyd-Jones D, Adams RJ, Brown TM et al. Heart disease and stroke statistics – 2010 update: a report from the American Heart Association. Circulation121(7), e46–e215 (2010).
   PubMed Web of Science ®Google Scholar
• Bonetti PO, Holmes DR Jr, Lerman A, Barsness GW. Enhanced external counterpulsation for ischemic heart disease: what’s behind the curtain?. J. Am. Coll. Cardiol.41(11), 1918–1925 (2003).
   PubMed Web of Science ®Google Scholar
• Elsman P, van‘t Hof AW, de Boer MJ et al. Role of collateral circulation in the acute phase of ST-segment-elevation myocardial infarction treated with primary coronary intervention. Eur. Heart J.25(10), 854–858 (2004).
   PubMedGoogle Scholar
• Habib GB, Heibig J, Forman SA et al.; TIMI Investigators. Influence of coronary collateral vessels on myocardial infarct size in humans. Results of Phase I Thrombolysis in Myocardial Infarction (TIMI) trial. Circulation83(3), 739–746 (1991).
   PubMed Web of Science ®Google Scholar
• Sabia PJ, Powers ER, Ragosta M, Sarembock IJ, Burwell LR, Kaul S. An association between collateral blood flow and myocardial viability in patients with recent myocardial infarction. N. Engl. J. Med.327(26), 1825–1831 (1992).
   PubMed Web of Science ®Google Scholar
• Harada K, Friedman M, Lopez JJ et al. Vascular endothelial growth factor administration in chronic myocardial ischemia. Am J. Physiol.270(5 Pt 2), H1791–H1802 (1996).
   PubMed Web of Science ®Google Scholar
• Laham RJ, Rezaee M, Post M et al. Intrapericardial delivery of fibroblast growth factor-2 induces neovascularization in a porcine model of chronic myocardial ischemia. J. Pharmacol. Exp. Ther.292(2), 795–802 (2000).
   PubMed Web of Science ®Google Scholar
• Lopez JJ, Laham RJ, Stamler A et al. VEGF administration in chronic myocardial ischemia in pigs. Cardiovasc. Res.40(2), 272–281 (1998).
   PubMed Web of Science ®Google Scholar
• Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, Verfaillie CM. Origin of endothelial progenitors in human postnatal bone marrow. J. Clin. Invest.109(3), 337–346 (2002).
   PubMed Web of Science ®Google Scholar
• Tepper OM, Capla JM, Galiano RD et al. Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow-derived cells. Blood105(3), 1068–1077 (2005).
   PubMed Web of Science ®Google Scholar
• Asahara T, Murohara T, Sullivan A et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science275(5302), 964–967 (1997).
   PubMed Web of Science ®Google Scholar
• Heil M, Eitenmuller I, Schmitz-Rixen T, Schaper W. Arteriogenesis versus angiogenesis: similarities and differences. J. Cell. Mol. Med.10(1), 45–55 (2006).
   PubMed Web of Science ®Google Scholar
• Morabito CJ, Dettman RW, Kattan J, Collier JM, Bristow J. Positive and negative regulation of epicardial–mesenchymal transformation during avian heart development. Dev. Biol.234(1), 204–215 (2001).
   Google Scholar
• Smart N, Dube KN, Riley PR. Coronary vessel development and insight towards neovascular therapy. Int. J. Exp. Pathol.90(3), 262–283 (2009).
   Google Scholar
• Meier P, Gloekler S, Zbinden R et al. Beneficial effect of recruitable collaterals: a 10-year follow-up study in patients with stable coronary artery disease undergoing quantitative collateral measurements. Circulation116(9), 975–983 (2007).
   PubMed Web of Science ®Google Scholar
• Boodhwani M, Sodha NR, Laham RJ, Sellke FW. The future of therapeutic myocardial angiogenesis. Shock26(4), 332–341 (2006).
   Google Scholar
• Losordo DW, Dimmeler S. Therapeutic angiogenesis and vasculogenesis for ischemic disease. Part I: angiogenic cytokines. Circulation109(21), 2487–2491 (2004).
   PubMed Web of Science ®Google Scholar
• Lazarous DF, Shou M, Stiber JA et al. Adenoviral-mediated gene transfer induces sustained pericardial VEGF expression in dogs: effect on myocardial angiogenesis. Cardiovasc. Res.44(2), 294–302 (1999).
   PubMed Web of Science ®Google Scholar
• Khan TA, Sellke FW, Laham RJ. Gene therapy progress and prospects: therapeutic angiogenesis for limb and myocardial ischemia. Gene Ther.10(4), 285–291 (2003).
   PubMed Web of Science ®Google Scholar
• Lavu M, Gundewar S, Lefer DJ. Gene therapy for ischemic heart disease. J. Mol. Cell Cardiol.50(5), 742–750 (2011).
   PubMed Web of Science ®Google Scholar
• Kastrup J, Jorgensen E, Ruck A et al. Direct intramyocardial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris. A randomized double-blind placebo-controlled study: the Euroinject One trial. J. Am. Coll. Cardiol.45(7), 982–988 (2005).
   PubMed Web of Science ®Google Scholar
• Kulkarni M, Greiser U, O’Brien T, Pandit A. Liposomal gene delivery mediated by tissue-engineered scaffolds. Trends Biotechnol.28(1), 28–36 (2010).
   PubMed Web of Science ®Google Scholar
• Deiner C, Schwimmbeck PL, Koehler IS et al. Adventitial VEGF165 gene transfer prevents lumen loss through induction of positive arterial remodeling after PTCA in porcine coronary arteries. Atherosclerosis189(1), 123–132 (2006).
   PubMed Web of Science ®Google Scholar
• Hedman M, Hartikainen J, Syvanne M et al. Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia: Phase II results of the Kuopio Angiogenesis Trial (KAT). Circulation107(21), 2677–2683 (2003).
   PubMed Web of Science ®Google Scholar
• Stewart DJ, Hilton JD, Arnold JM et al. Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a Phase 2 randomized, controlled trial of AdVEGF(121) (AdVEGF121) versus maximum medical treatment. Gene Ther.13(21), 1503–1511 (2006).
   PubMed Web of Science ®Google Scholar
• Baum C. Insertional mutagenesis in gene therapy and stem cell biology. Curr. Opin. Hematol.14(4), 337–342 (2007).
   PubMed Web of Science ®Google Scholar
• Pleger ST, Most P, Boucher M et al. Stable myocardial-specific AAV6-S100A1 gene therapy results in chronic functional heart failure rescue. Circulation115(19), 2506–2515 (2007).
   PubMed Web of Science ®Google Scholar
• Su H, Takagawa J, Huang Y et al. Additive effect of AAV-mediated angiopoietin-1 and VEGF expression on the therapy of infarcted heart. Int. J. Cardiol.133(2), 191–197 (2009).
   PubMed Web of Science ®Google Scholar
• Gaffney MM, Hynes SO, Barry F, O’Brien T. Cardiovascular gene therapy: current status and therapeutic potential. Br. J. Pharmacol.152(2), 175–188 (2007).
   PubMed Web of Science ®Google Scholar
• Baker AH. Designing gene delivery vectors for cardiovascular gene therapy. Prog. Biophys. Mol. Biol.84(2–3), 279–299 (2004).
   PubMed Web of Science ®Google Scholar
• Fortuin FD, Vale P, Losordo DW et al. One-year follow-up of direct myocardial gene transfer of vascular endothelial growth factor-2 using naked plasmid deoxyribonucleic acid by way of thoracotomy in no-option patients. Am. J. Cardiol.92(4), 436–439 (2003).
   PubMed Web of Science ®Google Scholar
• Grines C, Rubanyi GM, Kleiman NS, Marrott P, Watkins MW. Angiogenic gene therapy with adenovirus 5 fibroblast growth factor-4 (Ad5FGF-4): a new option for the treatment of coronary artery disease. Am. J. Cardiol.92(9B), N24–N31 (2003).
   PubMed Web of Science ®Google Scholar
• Grines CL, Watkins MW, Helmer G et al. Angiogenic Gene Therapy (AGENT) trial in patients with stable angina pectoris. Circulation105(11), 1291–1297 (2002).
   PubMed Web of Science ®Google Scholar
• Losordo DW, Vale PR, Hendel RC et al. Phase 1/2 placebo-controlled, double-blind, dose-escalating trial of myocardial vascular endothelial growth factor 2 gene transfer by catheter delivery in patients with chronic myocardial ischemia. Circulation105(17), 2012–2018 (2002).
   PubMed Web of Science ®Google Scholar
• Stewart DJ, Kutryk MJ, Fitchett D et al. VEGF gene therapy fails to improve perfusion of ischemic myocardium in patients with advanced coronary disease: results of the NORTHERN trial. Mol. Ther.17(6), 1109–1115 (2009).
   PubMed Web of Science ®Google Scholar
• Rissanen TT, Yla-Herttuala S. Current status of cardiovascular gene therapy. Mol. Ther.15(7), 1233–1247 (2007).
   PubMed Web of Science ®Google Scholar
• Henry TD, Grines CL, Watkins MW et al. Effects of Ad5FGF-4 in patients with angina: an analysis of pooled data from the AGENT-3 and AGENT-4 trials. J. Am. Coll. Cardiol.50(11), 1038–1046 (2007).
   PubMed Web of Science ®Google Scholar
• Putnam D. Polymers for gene delivery across length scales. Nat. Mater.5(6), 439–451 (2006).
   PubMed Web of Science ®Google Scholar
• Fishbein I, Alferiev IS, Nyanguile O et al. Bisphosphonate-mediated gene vector delivery from the metal surfaces of stents. Proc. Natl Acad. Sci. USA103(1), 159–164 (2006).
   PubMed Web of Science ®Google Scholar
• Sharif F, Hynes SO, McMahon J et al. Gene-eluting stents: comparison of adenoviral and adeno-associated viral gene delivery to the blood vessel wall in vivo. Hum. Gene Ther.17(7), 741–750 (2006).
   PubMed Web of Science ®Google Scholar
• Murohara T, Horowitz JR, Silver M et al. Vascular endothelial growth factor/vascular permeability factor enhances vascular permeability via nitric oxide and prostacyclin. Circulation97(1), 99–107 (1998).
   PubMed Web of Science ®Google Scholar
• Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science246(4935), 1306–1309 (1989).
   PubMed Web of Science ®Google Scholar
• Annex BH, Simons M. Growth factor-induced therapeutic angiogenesis in the heart: protein therapy. Cardiovasc. Res.65(3), 649–655 (2005).
   PubMed Web of Science ®Google Scholar
• Henry TD, Annex BH, McKendall GR et al. The VIVA trial: Vascular Endothelial Growth Factor in Ischemia for Vascular Angiogenesis. Circulation107(10), 1359–1365 (2003).
   PubMed Web of Science ®Google Scholar
• Simons M. Angiogenesis: where do we stand now?. Circulation111(12), 1556–1566 (2005).
   PubMed Web of Science ®Google Scholar
• Grines CL, Watkins MW, Mahmarian JJ et al. A randomized, double-blind, placebo-controlled trial of Ad5FGF-4 gene therapy and its effect on myocardial perfusion in patients with stable angina. J. Am. Coll. Cardiol.42(8), 1339–1347 (2003).
   PubMed Web of Science ®Google Scholar
• Boodhwani M, Voisine P, Ruel M et al. Comparison of vascular endothelial growth factor and fibroblast growth factor-2 in a swine model of endothelial dysfunction. Eur. J. Cardiothorac. Surg.33(4), 645–650 (2008).
   PubMed Web of Science ®Google Scholar
• Voisine P, Bianchi C, Ruel M et al. Inhibition of the cardiac angiogenic response to exogenous vascular endothelial growth factor. Surgery136(2), 407–415 (2004).
   PubMed Web of Science ®Google Scholar
• Boodhwani M, Sodha NR, Mieno S et al. Functional, cellular, and molecular characterization of the angiogenic response to chronic myocardial ischemia in diabetes. Circulation116(Suppl. 11), I31–I37 (2007).
   PubMed Web of Science ®Google Scholar
• Robich MP, Osipov RM, Nezafat R et al. Resveratrol improves myocardial perfusion in a swine model of hypercholesterolemia and chronic myocardial ischemia. Circulation122(Suppl. 11), S142–S149 (2010).
   PubMed Web of Science ®Google Scholar
• Boodhwani M, Sellke FW. Therapeutic angiogenesis in diabetes and hypercholesterolemia: influence of oxidative stress. Antioxid. Redox Signal.11(8), 1945–1959 (2009).
   PubMed Web of Science ®Google Scholar
• 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.296(2), H428–H434 (2009).
   PubMed Web of Science ®Google Scholar
• Boudoulas KD, Hatzopoulos AK. Cardiac repair and regeneration: the Rubik’s cube of cell therapy for heart disease. Dis. Model Mech.2(7–8), 344–358 (2009).
   PubMed Web of Science ®Google Scholar
• Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation105(1), 93–98 (2002).
   PubMed Web of Science ®Google Scholar
• Tomita S, Li RK, Weisel RD et al. Autologous transplantation of bone marrow cells improves damaged heart function. Circulation100(Suppl. 19), II247–II256 (1999).
   PubMed Web of Science ®Google Scholar
• Jiang Y, Jahagirdar BN, Reinhardt RL et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature418(6893), 41–49 (2002).
   PubMed Web of Science ®Google Scholar
• Shiota M, Heike T, Haruyama M et al. Isolation and characterization of bone marrow-derived mesenchymal progenitor cells with myogenic and neuronal properties. Exp. Cell Res.313(5), 1008–1023 (2007).
   Google Scholar
• Mieno S, Clements RT, Boodhwani M et al. Characteristics and function of cryopreserved bone marrow-derived endothelial progenitor cells. Ann. Thorac. Surg.85(4), 1361–1366 (2008).
   Google Scholar
• Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signaling and therapy. Circ. Res.103(11), 1204–1219 (2008).
   PubMed Web of Science ®Google Scholar
• Zhang Z, Deb A, Pachori A et al. Secreted frizzled related protein 2 protects cells from apoptosis by blocking the effect of canonical Wnt3a. J. Mol. Cell Cardiol.46(3), 370–377 (2009).
   Google Scholar
• Haider H, Jiang S, Idris NM, Ashraf M. IGF-1-overexpressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1alpha/CXCR4 signaling to promote myocardial repair. Circ. Res.103(11), 1300–1308 (2008).
   PubMed Web of Science ®Google Scholar
• Sun L, Cui M, Wang Z et al. Mesenchymal stem cells modified with angiopoietin-1 improve remodeling in a rat model of acute myocardial infarction. Biochem. Biophys. Res. Commun.357(3), 779–784 (2007).
   PubMed Web of Science ®Google Scholar
• Young PP, Vaughan DE, Hatzopoulos AK. Biologic properties of endothelial progenitor cells and their potential for cell therapy. Prog. Cardiovasc. Dis.49(6), 421–429 (2007).
   PubMed Web of Science ®Google Scholar
• Losordo DW, Dimmeler S. Therapeutic angiogenesis and vasculogenesis for ischemic disease: part II: cell-based therapies. Circulation109(22), 2692–2697 (2004).
   PubMed Web of Science ®Google Scholar
• Asahara T, Kawamoto A. Endothelial progenitor cells for postnatal vasculogenesis. Am. J. Physiol. Cell Physiol.287(3), C572–C579 (2004).
   PubMed Web of Science ®Google Scholar
• Kawamoto A, Asahara T, Losordo DW. Transplantation of endothelial progenitor cells for therapeutic neovascularization. Cardiovasc. Radiat. Med.3(3–4), 221–225 (2002).
   PubMedGoogle Scholar
• Krenning G, van Luyn MJ, Harmsen MC. Endothelial progenitor cell-based neovascularization: implications for therapy. Trends Mol. Med.15(4), 180–189 (2009).
   PubMedGoogle Scholar
• Beeres SL, Lamb HJ, Roes SD et al. Effect of intramyocardial bone marrow cell injection on diastolic function in patients with chronic myocardial ischemia. J. Magn. Reson. Imaging27(5), 992–997 (2008).
   Google Scholar
• Perin EC, Dohmann HF, Borojevic R et al. Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation110(11 Suppl. 1), II213–II218 (2004).
   PubMed Web of Science ®Google Scholar
• Kinnaird T, Stabile E, Burnett MS et al. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ. Res.94(5), 678–685 (2004).
   PubMed Web of Science ®Google Scholar
• Ziegelhoeffer T, Fernandez B, Kostin S et al. Bone marrow-derived cells do not incorporate into the adult growing vasculature. Circ. Res.94(2), 230–238 (2004).
   PubMed Web of Science ®Google Scholar
• Kupatt C, Horstkotte J, Vlastos GA et al. Embryonic endothelial progenitor cells expressing a broad range of proangiogenic and remodeling factors enhance vascularization and tissue recovery in acute and chronic ischemia. FASEB J.19(11), 1576–1578 (2005).
   PubMed Web of Science ®Google Scholar
• Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J. Cell. Biochem.98(5), 1076–1084 (2006).
   PubMed Web of Science ®Google Scholar
• Chen SY, Wang F, Yan XY et al. Autologous transplantation of EPCs encoding FGF1 gene promotes neovascularization in a porcine model of chronic myocardial ischemia. Int. J. Cardiol.135(2), 223–232 (2009).
   PubMed Web of Science ®Google Scholar
• Gnecchi M, He H, Noiseux N et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J.20(6), 661–669 (2006).
   PubMed Web of Science ®Google Scholar
• Li W, Ma N, Ong LL et al. Bcl-2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells25(8), 2118–2127 (2007).
   PubMed Web of Science ®Google Scholar
• Wernig M, Meissner A, Foreman R et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature448(7151), 318–324 (2007).
   PubMed Web of Science ®Google Scholar
• Huangfu D, Maehr R, Guo W et al. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat. Biotechnol.26(7), 795–797 (2008).
   PubMed Web of Science ®Google Scholar
• Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. Induced pluripotent stem cells generated without viral integration. Science322(5903), 945–949 (2008).
   PubMed Web of Science ®Google Scholar
• Singla DK, Hacker TA, Ma L et al. Transplantation of embryonic stem cells into the infarcted mouse heart: formation of multiple cell types. J. Mol. Cell Cardiol.40(1), 195–200 (2006).
   PubMed Web of Science ®Google Scholar
• Behfar A, Perez-Terzic C, Faustino RS et al. Cardiopoietic programming of embryonic stem cells for tumor-free heart repair. J. Exp. Med.204(2), 405–420 (2007).
   PubMed Web of Science ®Google Scholar
• Laflamme MA, Chen KY, Naumova AV et al. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat. Biotechnol.25(9), 1015–1024 (2007).
   PubMed Web of Science ®Google Scholar
• Tzahor E. Wnt/β-catenin signaling and cardiogenesis: timing does matter. Dev. Cell13(1), 10–13 (2007).
   PubMed Web of Science ®Google Scholar
• Yan P, Nagasawa A, Uosaki H et al. Cyclosporin-A potently induces highly cardiogenic progenitors from embryonic stem cells. Biochem. Biophys. Res. Commun.379(1), 115–120 (2009).
   Google Scholar
• Assmus B, Honold J, Schachinger V et al. Transcoronary transplantation of progenitor cells after myocardial infarction. N. Engl. J. Med.355(12), 1222–1232 (2006).
   PubMed Web of Science ®Google Scholar
• Lunde K, Solheim S, Aakhus S et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N. Engl. J. Med.355(12), 1199–1209 (2006).
   PubMed Web of Science ®Google Scholar
• Schachinger V, Erbs S, Elsasser A et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N. Engl. J. Med.355(12), 1210–1221 (2006).
   PubMed Web of Science ®Google Scholar
• Hirsch A, Nijveldt R, van der Vleuten PA et al. Intracoronary infusion of autologous mononuclear bone marrow cells in patients with acute myocardial infarction treated with primary PCI: pilot study of the multicenter HEBE trial. Catheter Cardiovasc. Interv.71(3), 273–281 (2008).
   PubMedGoogle Scholar
• Beitnes JO, Hopp E, Lunde K et al. Long-term results after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: the ASTAMI randomised, controlled study. Heart95(24), 1983–1989 (2009).
   PubMed Web of Science ®Google Scholar
• Tongers J, Losordo DW, Landmesser U. Stem and progenitor cell-based therapy in ischaemic heart disease: promise, uncertainties, and challenges. Eur. Heart J.32(10), 1197–1206 (2011).
   PubMed Web of Science ®Google Scholar
• Sun L, Bai Y, Du G. Endothelial dysfunction – an obstacle of therapeutic angiogenesis. Ageing Res. Rev.8(4), 306–313 (2009).
   Google Scholar
• Cohen DE, Melton D. Turning straw into gold: directing cell fate for regenerative medicine. Nat. Rev. Genet.12(4), 243–252 (2011).
   PubMed Web of Science ®Google Scholar
• Kiskinis E, Eggan K. Progress toward the clinical application of patient-specific pluripotent stem cells. J. Clin. Invest.120(1), 51–59 (2010).
   PubMed Web of Science ®Google Scholar
• Schussler O, Chachques JC, Mesana TG, Suuronen EJ, Lecarpentier Y, Ruel M. 3-dimensional structures to enhance cell therapy and engineer contractile tissue. Asian Cardiovasc. Thorac. Ann.18(2), 188–198 (2010).
   PubMedGoogle Scholar
• Segers VF, Lee RT. Stem-cell therapy for cardiac disease. Nature451(7181), 937–942 (2008).
   PubMed Web of Science ®Google Scholar
• Hagege AA, Marolleau JP, Vilquin JT et al. Skeletal myoblast transplantation in ischemic heart failure: long-term follow-up of the first Phase I cohort of patients. Circulation114(Suppl. 1), I108–I113 (2006).
   PubMed Web of Science ®Google Scholar
• Menasche P. Stem cell therapy for heart failure: are arrhythmias a real safety concern?. Circulation119(20), 2735–2740 (2009).
   PubMed Web of Science ®Google Scholar
• Coppen SR, Fukushima S, Shintani Y et al. A factor underlying late-phase arrhythmogenicity after cell therapy to the heart: global downregulation of connexin43 in the host myocardium after skeletal myoblast transplantation. Circulation118(Suppl. 14), S138–S144 (2008).
   Google Scholar
• Bhang SH, Cho SW, La WG et al. Angiogenesis in ischemic tissue produced by spheroid grafting of human adipose-derived stromal cells. Biomaterials32(11), 2734–2747 (2011).
   PubMed Web of Science ®Google Scholar
• Dinsmore JH, Dib N. Stem cell therapy for the treatment of acute myocardial infarction. Cardiol. Clin.28(1), 127–138 (2010).
   Google Scholar
• Orlandi A, Chavakis E, Seeger F, Tjwa M, Zeiher AM, Dimmeler S. Long-term diabetes impairs repopulation of hematopoietic progenitor cells and dysregulates the cytokine expression in the bone marrow microenvironment in mice. Basic Res. Cardiol.105(6), 703–712 (2010).
   PubMed Web of Science ®Google Scholar
• Tang C, Drukker M. Potential barriers to therapeutics utilizing pluripotent cell derivatives: intrinsic immunogenicity of in vitro maintained and matured populations. Semin. Immunopathol. DOI: 10.1007/s00281-011-0269-5 (2011) (Epub ahead of print).
   Google Scholar
• Gupta R, Tongers J, Losordo DW. Human studies of angiogenic gene therapy. Circ. Res.105(8), 724–736 (2009).
   PubMed Web of Science ®Google Scholar
• Lu H, Xu X, Zhang M et al. Combinatorial protein therapy of angiogenic and arteriogenic factors remarkably improves collaterogenesis and cardiac function in pigs. Proc. Natl Acad. Sci. USA104(29), 12140–12145 (2007).
   PubMed Web of Science ®Google Scholar
• Tang J, Wang J, Zheng F et al. Combination of chemokine and angiogenic factor genes and mesenchymal stem cells could enhance angiogenesis and improve cardiac function after acute myocardial infarction in rats. Mol. Cell. Biochem.339(1–2), 107–118 (2011).
   Google Scholar
• Bonaros N, Rauf R, Werner E et al. Neoangiogenesis after combined transplantation of skeletal myoblasts and angiopoietic progenitors leads to increased cell engraftment and lower apoptosis rates in ischemic heart failure. Interact. Cardiovasc. Thorac. Surg.7(2), 249–255 (2008).
   Google Scholar
• Guo YH, He JG, Wu JL et al. Hepatocyte growth factor and granulocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy. Cytotherapy10(8), 857–867 (2008).
   Web of Science ®Google Scholar
• Wang Y, Haider HK, Ahmad N, Xu M, Ge R, Ashraf M. Combining pharmacological mobilization with intramyocardial delivery of bone marrow cells over-expressing VEGF is more effective for cardiac repair. J. Mol. Cell Cardiol.40(5), 736–745 (2006).
   Google Scholar
• Sellke FW, Ruel M. Vascular growth factors and angiogenesis in cardiac surgery. Ann. Thorac. Surg.75(2), S685–S690 (2003).
   Google Scholar
• Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell75(5), 843–854 (1993).
   PubMed Web of Science ®Google Scholar
• Ambros V. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell113(6), 673–676 (2003).
   PubMed Web of Science ®Google Scholar
• Bushati N, Cohen SM. MicroRNA functions. Annu. Rev. Cell. Dev. Biol.23, 175–205 (2007).
   PubMed Web of Science ®Google Scholar
• Suarez Y, Sessa WC. MicroRNAs as novel regulators of angiogenesis. Circ. Res.104(4), 442–454 (2009).
   PubMed Web of Science ®Google Scholar
• Chang TC, Mendell JT. microRNAs in vertebrate physiology and human disease. Annu. Rev. Genomics Hum. Genet.8, 215–239 (2007).
   PubMed Web of Science ®Google Scholar
• van Rooij E, Olson EN. MicroRNAs: powerful new regulators of heart disease and provocative therapeutic targets. J. Clin. Invest.117(9), 2369–2376 (2007).
   PubMed Web of Science ®Google Scholar
• Silvestri P, Di Russo C, Rigattieri S et al. MicroRNAs and ischemic heart disease: towards a better comprehension of pathogenesis, new diagnostic tools and new therapeutic targets. Recent Pat. Cardiovasc. Drug Discov.4(2), 109–118 (2009).
   PubMedGoogle Scholar
• Port JD, Sucharov C. Role of microRNAs in cardiovascular disease: therapeutic challenges and potentials. J. Cardiovasc. Pharmacol.56(5), 444–453 (2010).
   PubMed Web of Science ®Google Scholar
• Suarez Y, Fernandez-Hernando C, Pober JS, Sessa WC. Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ. Res.100(8), 1164–1173 (2007).
   PubMed Web of Science ®Google Scholar
• Fasanaro P, D’Alessandra Y, Di Stefano V et al. MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J. Biol. Chem.283(23), 15878–15883 (2008).
   PubMed Web of Science ®Google Scholar
• Small EM, Frost RJ, Olson EN. MicroRNAs add a new dimension to cardiovascular disease. Circulation121(8), 1022–1032 (2010).
   PubMed Web of Science ®Google Scholar
• le Sage C, Nagel R, Egan DA et al. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J.26(15), 3699–3708 (2007).
   PubMed Web of Science ®Google Scholar
• O’Reilly MS, Boehm T, Shing Y et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell88(2), 277–285 (1997).
   PubMed Web of Science ®Google Scholar
• O’Reilly MS, Holmgren L, Shing Y et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell79(2), 315–328 (1994).
   PubMed Web of Science ®Google Scholar
• Troyanovsky B, Levchenko T, Mansson G, Matvijenko O, Holmgren L. Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation. J. Cell. Biol.152(6), 1247–1254 (2001).
   PubMed Web of Science ®Google Scholar
• Dixelius J, Cross M, Matsumoto T, Sasaki T, Timpl R, Claesson-Welsh L. Endostatin regulates endothelial cell adhesion and cytoskeletal organization. Cancer Res.62(7), 1944–1947 (2002).
   PubMed Web of Science ®Google Scholar
• Kim YM, Hwang S, Pyun BJ et al. Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1. J. Biol. Chem.277(31), 27872–27879 (2002).
   PubMed Web of Science ®Google Scholar
• Nyberg P, Xie L, Kalluri R. Endogenous inhibitors of angiogenesis. Cancer Res.65(10), 3967–3979 (2005).
   PubMed Web of Science ®Google Scholar
• Robich MP, Chu LM, Chaudray M et al. Anti-angiogenic effect of high-dose resveratrol in a swine model of metabolic syndrome. Surgery148(2), 453–462 (2010).
   Google Scholar
• Heba G, Krzeminski T, Porc M, Grzyb J, Ratajska A, Dembinska-Kiec A. The time course of tumor necrosis factor-α, inducible nitric oxide synthase and vascular endothelial growth factor expression in an experimental model of chronic myocardial infarction in rats. J. Vasc. Res.38(3), 288–300 (2001).
   PubMed Web of Science ®Google Scholar
• Matsunaga T, Chilian WM, March K. Angiostatin is negatively associated with coronary collateral growth in patients with coronary artery disease. Am. J. Physiol. Heart Circ. Physiol.288(5), H2042–H2046 (2005).
   Google Scholar
• Suuronen EJ, Hazra S, Zhang P et al. Impairment of human cell-based vasculogenesis in rats by hypercholesterolemia-induced endothelial dysfunction and rescue with L-arginine supplementation. J. Thorac. Cardiovasc. Surg.139(1), 209–216.e202 (2010).
   PubMed Web of Science ®Google Scholar
• Boodhwani M, Nakai Y, Mieno S et al. Hypercholesterolemia impairs the myocardial angiogenic response in a swine model of chronic ischemia: role of endostatin and oxidative stress. Ann. Thorac. Surg.81(2), 634–641 (2006).
   PubMed Web of Science ®Google Scholar
• Boodhwani M, Nakai Y, Voisine P et al. High-dose atorvastatin improves hypercholesterolemic coronary endothelial dysfunction without improving the angiogenic response. Circulation114(Suppl. 1), I402–I408 (2006).
   Google Scholar
• Sodha NR, Boodhwani M, Clements RT, Xu SH, Khabbaz KR, Sellke FW. Increased antiangiogenic protein expression in the skeletal muscle of diabetic swine and patients. Arch. Surg.143(5), 463–470 (2008).
   PubMedGoogle Scholar
• Boodhwani M, Mieno S, Voisine P et al. High-dose atorvastatin is associated with impaired myocardial angiogenesis in response to vascular endothelial growth factor in hypercholesterolemic swine. J. Thorac. Cardiovasc. Surg.132(6), 1299–1306 (2006).
   Google Scholar
• Elliott PJ, Jirousek M. Sirtuins: novel targets for metabolic disease. Curr. Opin. Investig. Drugs9(4), 371–378 (2008).
   PubMed Web of Science ®Google Scholar
• Antoniades C, Tousoulis D, Tountas C et al. Vascular endothelium and inflammatory process, in patients with combined Type 2 diabetes mellitus and coronary atherosclerosis: the effects of vitamin C. Diabet. Med.21(6), 552–558 (2004).
   PubMed Web of Science ®Google Scholar
• Gupta S, Sodhi S, Mahajan V. Correlation of antioxidants with lipid peroxidation and lipid profile in patients suffering from coronary artery disease. Expert Opin. Ther. Targets13(8), 889–894 (2009).
   PubMed Web of Science ®Google Scholar
• Libby P, Aikawa M. Mechanisms of plaque stabilization with statins. Am. J. Cardiol.91(4A), B4–B8 (2003).
   Web of Science ®Google Scholar
• Lavu S, Boss O, Elliott PJ, Lambert PD. Sirtuins – novel therapeutic targets to treat age-associated diseases. Nat. Rev. Drug Discov.7(10), 841–853 (2008).
   PubMed Web of Science ®Google Scholar
• Sodha NR, Chu LM, Boodhwani M, Sellke FW. Pharmacotherapy for end-stage coronary artery disease. Expert Opin. Pharmacother.11(2), 207–213 (2010).
   PubMed Web of Science ®Google Scholar
• Niu G, Chen X. PET imaging of angiogenesis. PET Clin.4(1), 17–38 (2009).
   PubMedGoogle Scholar
• Oostendorp M, Douma K, Wagenaar A et al. Molecular magnetic resonance imaging of myocardial angiogenesis after acute myocardial infarction. Circulation121(6), 775–783 (2010).
   Google Scholar
• Wykrzykowska JJ, Henry TD, Lesser JR, Schwartz RS. Imaging myocardial angiogenesis. Nat. Rev. Cardiol.6(10), 648–658 (2009).
   PubMed Web of Science ®Google Scholar
• Li Z, Lee A, Huang M et al. Imaging survival and function of transplanted cardiac resident stem cells. J. Am. Coll. Cardiol.53(14), 1229–1240 (2009).
   PubMed Web of Science ®Google Scholar
• Rana JS, Mannam A, Donnell-Fink L, Gervino EV, Sellke FW, Laham RJ. Longevity of the placebo effect in the therapeutic angiogenesis and laser myocardial revascularization trials in patients with coronary heart disease. Am. J. Cardiol.95(12), 1456–1459 (2005).
   PubMed Web of Science ®Google Scholar