Skip to main content
Article thumbnail
Location of Repository

A Pre-clinical Evaluation of Growth Factor-eluting Stents for the Treatment of Chronic Total Coronary Artery Occlusion

By Damian John Kelly


Objectives: Chronic total coronary artery occlusion (CTO) remains a significant challenge for percutaneous coronary intervention. Using a novel endovascular porcine model of coronary occlusion we investigated a strategy of promoting antegrade collateral vessels without crossing the occlusion. The prolyl-4-hydroxylase inhibitor, dimethyl\ud oxalyl glycine (DMOG) was used to up-regulate a pro-angiogenic transcription factor, hypoxia inducible factor-1α.\ud Method: DMOG was loaded onto a polymer-coated coronary stent. We developed a novel, entirely endovascular, method of inducing a coronary occlusion. Copper-coated stents were delivered percutaneously to produce CTO lesions in 20 Yorkshire white pigs. DMOG stents were implanted at day 28 and angiographic and physiological data collected on distal coronary and collateral flow. At day 56 the animals were sacrificed and histological analysis performed.\ud Results: A complete total coronary occlusion was present in all animals at day 28 following implantation of a copper stent. At 56 days there was a greater percentage increase in angiographic collateral area in the DMOG group compared with the control (polymer-only stent) group (84.5±34.5% versus 16.5±5.9%, p=0.057). There was no difference between the groups in a surrogate measure of collateral flow at day 56. Histology revealed a significant increase in collateral vessels around the site of occlusion in the DMOG group compared with controls (29.9±2.6 versus 18.4±3.1, p=0.01).\ud Conclusions: DMOG increased the number of collateral vessels at the site of vessel occlusion but not in the distal vessel. The angiogenic effect of DMOG appeared to be restricted to ischaemic tissue. Implantation of a copper stent provides a reliable entirely endovascular method of producing a CTO, with marked antegrade collateral formation present at 28 days. Proximal placement of stents delivering angiogenic compounds such as DMOG may provide a clinical management option in resistant CTO lesion

Publisher: University of Leicester
Year: 2010
OAI identifier:

Suggested articles


  1. (2009). 2-year outcomes and results from multiple imaging methods 1. Lancet
  2. A bioabsorbable everolimus-eluting coronary stent system
  3. (1993). A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group 9.
  4. (2004). A method for the isolation of glomerular and tubulointerstitial endothelial cells and a comparison of characteristics with the human umbilical vein endothelial cell model 2. Nephrology (Carlton )
  5. (1993). A model to assess interventions to improve collateral blood flow: continuous administration of agents into the left coronary artery in dogs 4. Cardiovasc Res
  6. (2005). A new percutaneous porcine coronary model of chronic total occlusion.
  7. (2007). A novel class of prolyl hydroxylase inhibitors induces angiogenesis and exerts organ protection against ischemia 5. Arterioscler Thromb Vasc Biol
  8. (1992). A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation 18.Mol Cell Biol
  9. A Porcine Endovascular Model Of A Chronic Total Coronary Artery Occlusion. Heart 94, A85. 5-10-2008. Ref Type: Abstract
  10. (2002). A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization.
  11. (1999). A randomized trial of elective stenting after balloon recanalization of chronic total occlusions.
  12. (2003). A randomized, double-blind, placebo-controlled trial of Ad5FGF-4 gene therapy and its effect on myocardial perfusion in patients with stable angina.
  13. (2006). A randomized, doubleblind, placebo-controlled, multicenter, pilot study of the safety and feasibility of catheter-based intramyocardial injection of AdVEGF121 in patients with refractory advanced coronary artery disease. Catheter Cardiovasc Interv
  14. (1992). A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor 3. Lab Invest
  15. (1992). A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor 77. Lab Invest
  16. (2005). Activation of hypoxia-inducible factors in hyperoxia through prolyl 4-hydroxylase blockade in cells and explants of primate lung.
  17. (2003). Activation of the hypoxia-inducible factor-pathway and stimulation of angiogenesis by application of prolyl hydroxylase inhibitors 2.
  18. (1996). Activation of vascular endothelial growth factor gene transcription by hypoxiainducible factor 1 292.Molecular & Cellular Biology
  19. (1995). Activation-dependent isolation and culture of murine pulmonary microvascular endothelium 4.Microcirculation
  20. (1999). Acute results of biodegradable poly-l-lactic acid coronary stents in humans: an alternative to metallic stents?
  21. (1969). Ameroid constrictor: uniform closure rates and a calibration procedure 5.
  22. (1993). An animal model of coronary thrombosis and thrombolysis--comparisons of vascular damage and thrombus formation in the coronary and femoral arteries after balloon angioplasty 2. Jpn Circ J
  23. (2007). An endoplasmic reticulum transmembrane prolyl 4-hydroxylase is induced by hypoxia and acts on hypoxia-inducible factor alpha 1.
  24. An ex vivo angiogenesis assay utilizing commercial porcine carotid artery: modification of the rat aortic ring assay.
  25. (1999). An in vitro model of angiogenesis: basic features 1. Angiogenesis
  26. (2003). Angiogenesis assays: a critical overview 5. Clin Chem
  27. Angiogenesis assays: problems and pitfalls 6. Cancer Metastasis Rev
  28. (2006). Angiogenesis Assays.
  29. (2003). Angiogenesis in health and disease. Nat Med
  30. (1980). Angiogenesis in vitro 3. Nature
  31. (2000). Angiogenesis is induced in a rabbit model of hindlimb ischemia by naked DNA encoding an HIF-1alpha/VP16 hybrid transcription factor 147. Circulation
  32. (1997). Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha1beta1 and alpha2beta1 integrins.
  33. (2006). Angiogenesis: bench to bedside, have we learned anything? 1. Toxicol Pathol
  34. Angiogenic Gene Therapy
  35. Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a phase 2 randomized, controlled trial of AdVEGF(121)
  36. (1993). Angiogenic role of endogenous basic fibroblast growth factor released by rat aorta after injury 6.
  37. (1994). Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs 91. Circulation
  38. (1982). Angiographic findings 1 month after myocardial infarction: a prospective study of 259 survivors 9. Circulation
  39. (1993). Angiographic suitability for catheter revascularization of total coronary occlusions in patients from a community hospital setting.
  40. (1985). Angioplasty in total coronary artery occlusion: experience in 76 consecutive patients.
  41. (2008). Appendix 1- Publications to date from this thesis Abstracts: Increased Endothelial Cell Mobility Following Stabilization of Hypoxia-Inducible Factor-Steps Towards Therapeutic Angiogenesis.
  42. (1997). Arterial gene transfer of acidic fibroblast growth factor for therapeutic angiogenesis in vivo: critical role of secretion signal in use of naked DNA 1. Cardiovasc Res
  43. (2003). Arteriogenesis induced by intramyocardial vascular endothelial growth factor 165 gene transfer in chronically ischemic pigs. Hum Gene Ther
  44. (1997). Atherosclerosis and angiogenesis. Its pathophysiological significance in humans as well as in an animal model induced by the gene transfer of vascular endothelial growth factor 60.
  45. (1986). Basement membrane complexes with biological activity. Biochemistry
  46. (2003). Basement membranes: structure, assembly and role in tumour angiogenesis 2. Nat Rev Cancer
  47. (1994). Basic fibroblast growth factor enhances myocardial collateral flow in a canine model 3.
  48. (1994). Basic fibroblast growth factor improves myocardial function in chronically ischemic porcine hearts 2.
  49. (1997). Basic fibroblast growth factor in a porcine model of chronic myocardial ischemia: a comparison of angiographic, echocardiographic and coronary flow parameters 159.
  50. (1998). Biologic bypass with the use of adenovirusmediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart 5. J Thorac Cardiovasc Surg
  51. (1999). Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization 24. Circ Res
  52. (2000). Carboxyamido-triazole inhibits angiogenesis by blocking the calcium-mediated nitric-oxide synthasevascular endothelial growth factor pathway 1. J Pharmacol Exp Ther
  53. (2004). Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases.
  54. (2000). Catheter-based endomyocardial injection of viral or plasmid DNA in vivo stimulates local VEGF production irrespective of the gene delivered.
  55. (2000). Catheter-based plasmid-mediated transfer of genes into ischemic myocardium using the pCOR plasmid 52. Coron Artery Dis
  56. (2000). Catheter-based transendocardial gene delivery for therapeutic myocardial angiogenesis 37.
  57. (2002). Caveolin-1 expression enhances endothelial capillary tubule formation 12.
  58. (2003). Cell type-specific regulation of 55. Circ Res
  59. (1998). Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha 2. Genes Dev
  60. (2004). Chemical suppression of a genetic mutation in a zebrafish model of aortic coarctation 17. Nat Biotechnol
  61. (2009). Chronic total occlusions.
  62. (1996). Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet
  63. (2001). Clinical outcome of a cohort of patients eligible for therapeutic angiogenesis or transmyocardial revascularization 16. Am Heart J
  64. (2005). Clinical progression of incidental, asymptomatic lesions discovered during culprit vessel coronary intervention. Circulation
  65. Cloning and characterization of vascular endothelial growth factor
  66. (2003). Collagenase plaque digestion for facilitating guide wire crossing in chronic total occlusions 3. Circulation
  67. Combined gene therapy with TMR improves hemodynamic performance in chronically ischemic porcine hearts 384. American Heart Association , 1125. 9-11-1998. Ref Type: Abstract
  68. (1996). Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury 1. Circulation
  69. (2002). Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction.
  70. Comparison of three in vitro human 'angiogenesis' assays with capillaries formed in vivo 1.
  71. (1998). Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation
  72. (2001). Continued benefit of coronary stenting versus balloon angioplasty: five-year clinical follow-up of Benestent-I trial.
  73. (1998). Controlled delivery of vascular endothelial growth factor promotes neovascularization and maintains limb function in a rabbit model of ischemia 309.
  74. (1987). Controlled-release drug delivery of diphosphonates to inhibit bioprosthetic heart valve calcification: release rate modulation with silicone matrices via drug solubility and membrane coating 280.
  75. (1999). Coronary artery expression of VEGF after balloon angioplasty correlates with vasa vasorum angiogenesis: potential role in arterial remodelling.
  76. (2006). Coronary intervention for persistent occlusion after myocardial infarction 13.
  77. (1997). Correlations between recruitable coronary collateral flow velocities, distal occlusion pressure, and electrocardiographic changes in patients undergoing angioplasty 2. Jpn Circ J
  78. (1973). Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria 16.
  79. (2004). Current methods for assaying angiogenesis in vitro and in vivo 159. Int J Exp Pathol
  80. (1994). Current status of biodegradable stents 5. Cardiol Clin
  81. (1998). Danio rerio 6. Biochim Biophys Acta
  82. (2002). Development of a computer-assisted high-throughput screening platform for anti-angiogenic testing 1.Microvasc Res
  83. (2008). Development of a novel calcified total occlusion model in porcine coronary arteries 17. J Invasive Cardiol
  84. (2009). Development of animal model for calcified chronic total occlusion 1. Catheter Cardiovasc Interv
  85. (1996). Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion 311. Circulation
  86. (2005). Direct intramyocardial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris A randomized doubleblind placebo-controlled study: the Euroinject One trial.
  87. (2002). Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels 2. Development
  88. (2000). Distinct requirements for zebrafish angiogenesis revealed by a VEGF-A morphant 4. Yeast
  89. Drug-eluting stents: are they really safe? 149. Am Heart Hosp
  90. (1998). Early events in angiogenesis: cloning an alpha-prolyl 4-hydroxylase-like gene 1.
  91. (1997). Effect of basic fibroblast growth factor on myocardial angiogenesis in dogs with mature collateral vessels 4.
  92. (1995). Effect of infarct artery patency on prognosis after acute myocardial infarction. The Survival and Ventricular Enlargement Investigators. Circulation
  93. (2000). Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion: evidence for a dosedependent effect 2. Circulation
  94. (1954). Effect of oxygen on developing retinal vessels with particular reference to the problem of retrolental fibroplasia 1.
  95. (2003). Effect of recanalization of chronic total occlusions on global and regional left ventricular function in patients with or without previous myocardial infarction 3. Catheter Cardiovasc Interv
  96. (1991). Effects of acidic fibroblast growth factor on normal and ischemic myocardium 4. Circ Res
  97. (1993). Effects of angiotensin converting enzyme inhibition on neointimal proliferation in a porcine coronary injury model 1. Am Heart J
  98. (1995). Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart 2. Circulation
  99. (1997). Effects of cytogenin, a novel microbial product, on embryonic and tumor cell-induced angiogenic responses in vivo 1. Anticancer Res
  100. (1997). Effects of high glucose on vascular endothelial growth factor expression in vascular smooth muscle cells 691.
  101. (2001). Effects of intramyocardial injection of phVEGF-A165 as sole therapy in patients with refractory coronary artery disease--12-month follow-up: angiogenic gene therapy.
  102. (1999). Endogenous, local, vascular endothelial growth factor production in patients with chronic total coronary occlusion: further evidence of its role in angiogenesis.
  103. (2000). Endostatin inhibits microvessel formation in the ex vivo rat aortic ring angiogenesis assay 2. Biochem Biophys Res Commun
  104. (2009). Endothelial cell biology.
  105. (2004). Endothelial cell culture: beginnings of modern vascular biology 1.
  106. Endothelial cell-matrix interactions.
  107. (1998). Endothelial cells in physiology and in the pathophysiology of vascular disorders 2. Blood
  108. (2005). Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) Registry 12.
  109. Endothelium in vitro: a review of human vascular endothelial cell lines for blood vessel-related research 6.
  110. (1996). Enhanced microvascular relaxations to VEGF and bFGF in chronically ischemic porcine myocardium 75.
  111. (2008). European experience with the retrograde approach for the recanalisation of coronary artery chronic total occlusions. A report on behalf of the euroCTO club 1. EuroIntervention
  112. (2001). Evaluation of endovascular techniques for creating a porcine femoral artery occlusion model 4. J Endovasc Ther
  113. (1985). Evaluation of in vivo adsorption of blood elements onto hydrogel-coated silicone rubber by scanning electron microscopy and fourier transform infrared spectroscopy 1.
  114. (2005). Expression and purification of the catalytic domain of human vascular endothelial growth factor receptor 2 for inhibitor screening 5. Biochim Biophys Acta
  115. (2002). Expression of the angiopoietins and their receptor Tie2 in human renal clear cell carcinomas; regulation by the von Hippel-Lindau gene and hypoxia 23. J Pathol
  116. (2001). Expression of vascular endothelial growth factor and its receptors is increased, but microvascular relaxation is impaired in patients after acute myocardial ischemia 158. J Thorac Cardiovasc Surg
  117. (2000). Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors 1. Blood
  118. (2009). first-in-man study: 6-month results of a biodegradable polymer sustained release tacrolimus-eluting stent in de novo coronary stenoses 4. Eur Heart J
  119. (2000). Focal angiogen therapy using intramyocardial delivery of an adenovirus vector coding for vascular endothelial growth factor 121 1. Ann Thorac Surg
  120. (1998). Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation
  121. (1999). Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease. Ann Thorac Surg
  122. (2000). Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences 1. Nat Genet
  123. (1996). Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo 76. Laboratory Investigation
  124. (1996). Gershlick AH. Antithrombotic potential of polymer-coated stents eluting platelet glycoprotein IIb/IIIa receptor antibody 34. Circulation
  125. (1994). Giaccia AJ. Hypoxia induces accumulation of p53 protein, but activation of a G1-phase checkpoint by low-oxygen conditions is independent of p53 status 16.Mol Cell Biol
  126. (1998). Green mice' and their potential usage in biological research 69. FEBS Lett
  127. (2005). Griffioen AW. In silico analysis of angiogenesis associated gene expression identifies angiogenic stage related profiles 11. Biochim Biophys Acta
  128. (1990). Growth of microvessels in serum-free matrix culture of rat aorta. A quantitative assay of angiogenesis in vitro 1. Lab Invest
  129. (2003). heart of glass regulates the concentric growth of the heart in zebrafish 2. Curr Biol
  130. (1997). Hemodynamic effects of intracoronary VEGF delivery: evidence of tachyphylaxis and NO dependence of response 2.
  131. (1996). Heparin-coated Palmaz-Schatz stents in human coronary arteries. Early outcome of the Benestent-II Pilot Study 9. Circulation
  132. (1997). Heparin-Coated Stents Eliminate Mural Thrombus Deposition for Days Without Affecting Restenosis. Circulation
  133. (2007). HIF prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques 1. Blood
  134. (1997). Histologic correlates of angiographic chronic total coronary artery occlusions: influence of occlusion duration on neovascular channel patterns and intimal plaque composition.
  135. (2004). Hydroxylation of HIF-1: oxygen sensing at the molecular level 2. Physiology (Bethesda )
  136. (1997). Hypercholesterolemia attenuates angiogenesis but does not preclude augmentation by angiogenic cytokines 3. Circulation
  137. (1995). Hypoxia induces vascular endothelial growth factor in cultured human endothelial cells 82.
  138. (2006). Hypoxia inducible factor-1 activation by prolyl 4-hydroxylase-2 gene silencing attenuates myocardial ischemia reperfusion injury 4. Circ Res
  139. (1995). Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5' enhancer 1. Circ Res
  140. (1992). Identification of multiple active growth factors in basement membrane Matrigel suggests caution in interpretation of cellular activity related to extracellular matrix components 106. Exp Cell Res
  141. (1999). Images in Cardiovascular Medicine: Percutaneous myocardial gene transfer of phVEGF-2 4. Circulation
  142. (2003). Immediate results and oneGISE).
  143. (2003). Impact of age on procedural and 1-year outcome in percutaneous transluminal coronary angioplasty: a report from the NHLBI Dynamic Registry 6. Am Heart J
  144. (2006). Implantation of oxygen enhanced, three-dimensional microporous L-PLA polymers: a reproducible porcine model of chronic total coronary occlusion 1. Catheter Cardiovasc Interv
  145. (1998). Improvement in left ventricular ejection fraction and wall motion after successful recanalization of chronic coronary occlusions 5. Eur Heart J
  146. (2003). In vivo chamber angiogenesis assay: an optimized Matrigel plug assay for fast assessment of anti-angiogenic activity 2.
  147. (1996). In vivo evaluation of a fluorine-acryl-stylene-urethane-silicone antithrombogenic coating material copolymer for intravascular stents. Academic Radiology
  148. (2002). In vivo imaging of embryonic vascular development using transgenic zebrafish 12. Dev Biol
  149. (2009). Incomplete revascularization in the era of drug-eluting stents: impact on adverse outcomes 1. JACC Cardiovasc Interv
  150. (2001). Increases Neovascularization Within Ischaemic Myocardium in a Porcine Coronary Occlusion
  151. (2001). Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1alpha 1. Genes Dev
  152. (1998). Induction of macrophage VEGF in response to oxidized LDL and VEGF accumulation in human atherosclerotic lesions. Arteriosclerosis, Thrombosis & Vascular Biology
  153. (1989). Induction of morphologic differentiation of endothelial cells
  154. (1997). Induction of vascular endothelial growth factor in balloon-injured baboon arteries. A novel role for reactive oxygen species in atherosclerosis 160. Circulation Research
  155. (2004). Inhibition of endogenous HIF inactivation induces angiogenesis in ischaemic skeletal muscles of mice.
  156. (1999). Inhibition of intimal thickening after balloon angioplasty in porcine coronary arteries by targeting regulators of the cell cycle. Circulation
  157. (2002). Inhibition of programmed cell death impairs in vitro vascular-like structure formation and reduces in vivo angiogenesis 1.
  158. (2004). Inhibition of the cardiac angiogenic response to exogenous vascular endothelial growth factor 12. Surgery
  159. (2003). Initial experience and safety in the treatment of chronic total coronary occlusions with a new optical coherent reflectometry-guided radiofrequency ablation guidewire 18.
  160. (2000). Insights into early vasculogenesis revealed by expression of the ETS-domain transcription factor Fli-1 in wild-type and mutant zebrafish embryos 1.Mech Dev
  161. (2009). Interferon-gamma induces prolyl hydroxylase (PHD)3 through a STAT1-dependent mechanism in human endothelial cells 1. Arterioscler Thromb Vasc Biol
  162. (1991). Intracellular mechanisms involved in basement membrane induced blood vessel differentiation in vitro 2.
  163. (2001). Intracoronary administration of recombinant human vascular endothelial growth factor to patients with coronary artery disease 1. Am Heart J
  164. (1999). Intracoronary and intravenous administration of basic fibroblast growth factor: myocardial and tissue distribution 4. Drug Metab Dispos
  165. (2000). Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a phase I open-label dose escalation study 3.
  166. (2000). Intracoronary basic fibroblast growth factor enhances myocardial collateral perfusion in dogs 1.
  167. (1996). Intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart 1. Nat Med
  168. (1994). Intramuscular administration of vascular endothelial growth factor induces dose-dependent collateral artery augmentation in a rabbit model of chronic limb ischemia 315. Circulation
  169. (2000). Intramuscular gene transfer of VEGF165 in rabbit model of hind-limb ischemia.
  170. (2009). Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA
  171. (1999). Intramyocardial gene therapy with naked DNA encoding vascular endothelial growth factor improves collateral flow to ischemic myocardium 1. Hum Gene Ther
  172. (2002). Intramyocardial injection of naked DNA encoding HIF-1alpha/VP16 hybrid to enhance angiogenesis in an acute myocardial infarction model in the rat 1. Cardiovasc Res
  173. (2006). Intramyocardial injection of vascular endothelial growth factor-A165 plasmid followed by granulocyte-colony stimulating factor to induce angiogenesis in patients with severe chronic ischaemic heart disease. Eur Heart J
  174. (2007). Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation
  175. (2000). Intrapericardial delivery of fibroblast growth factor-2 induces neovascularization in a porcine model of chronic myocardial ischemia 3. J Pharmacol Exp Ther
  176. (1999). Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization 7. Nat Med
  177. (1971). Isolation of a tumor factor responsible for angiogenesis 2. J Exp Med
  178. (2005). Kukreja RC. HIF-1 activation attenuates postischemic myocardial injury: role for heme oxygenase-1 in modulating microvascular chemokine generation. Am J Physiol Heart Circ Physiol
  179. (1998). Local administration of L-703,081 Using a Composite Polymeric Stent Reduces Platelet Deposition in Canine Coronary Arteries.
  180. (1994). Local drug delivery for the prevention of restenosis. Fact, fancy, and future. 305. Circulation
  181. (1996). Local methylprednisolone inhibition of foreign body response to coated intracoronary stents 7. Coronary Artery Disease
  182. (1999). Local perivascular delivery of basic fibroblast growth factor in patients undergoing coronary bypass surgery: results of a phase I randomized, double-blind, placebo-controlled trial. Circulation
  183. Localisation of the vascular endothelial growth factor A,B,C and their receptors in human atherosclerotic arteries.
  184. (1996). Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3 3. Cell
  185. (2005). Long-term (2-year) clinical events following transthoracic intramyocardial gene transfer of VEGF-2 in no-option patients 1. J Interv Cardiol
  186. (2007). Long-term clinical outcomes with sirolimuseluting coronary stents: five-year results of the RAVEL trial.
  187. (1994). Long-term prognostic importance of patency of the infarct-related coronary artery after thrombolytic therapy for acute myocardial infarction. Circulation
  188. (2005). Longevity of the placebo effect in the therapeutic angiogenesis and laser myocardial revascularization trials in patients with coronary heart disease 1.
  189. (2000). Lower-extremity edema associated with gene transfer of naked DNA encoding vascular endothelial growth factor 107. Ann Intern Med
  190. (1995). Magnetic resonance mapping demonstrates benefits of VEGF-induced myocardial angiogenesis 910. Nature Medicine
  191. (2005). Maintenance of long-term clinical benefit with sirolimus-eluting coronary stents: three-year results of the RAVEL trial. Circulation
  192. (1957). Mechanism of the erythropoietic effect of cobalt 174. Science
  193. (1992). Media conditioned by smooth muscle cells cultured in a variety of hypoxic environments stimulates in vitro angiogenesis. A relationship to transforming growth factor-beta 1.
  194. (2005). Microvessels in chronic total occlusions: pathways for successful guidewire crossing? 131. J Interv Cardiol
  195. (2001). Mobilization of endothelial progenitor cells in patients with acute myocardial infarction 18. Circulation
  196. (1995). Models of in vitro angiogenesis: endothelial cell differentiation on fibrin but not matrigel is transcriptionally dependent 1. Biochem Biophys Res Commun
  197. (2005). Molecular cloning and expression of a novel CYP26 gene (cyp26d1) during zebrafish early development 27. Gene Expr Patterns
  198. (2005). Multiple fragments related to angiostatin and endostatin in fluid from venous leg ulcers 1.Wound Repair Regen
  199. (2001). Myocardial Doppler tissue velocity improves following myocardial gene therapy with VEGF-A165 plasmid in patients with inoperable angina pectoris. Coron Artery Dis
  200. (2001). Myocardial perfusion in patients with total occlusion of a single coronary artery with and without collateral circulation 71.
  201. (1998). Myocardial VEGF expression after cardiopulmonary bypass and cardioplegia 4. Circulation
  202. (1996). Neointimal thickening after severe coronary artery injury is limited by a short-term administration of a factor Xa inhibitor. Results in a porcine model 2. Circulation
  203. (2003). Not just angiogenesis--wider roles for the angiopoietins 7.
  204. (2001). Notch signaling is required for arterial-venous differentiation during embryonic vascular development 1. Development
  205. (2008). Novel drug eluting stent system for customised treatment of coronary lesions: CUSTOM I feasibility trial 24 month results 1. EuroIntervention
  206. (2005). of Cardiology PCI Audit Group. Euro Heart Survey 3rd report.
  207. (2009). One step forward and two steps back with drug-eluting-stents: from preventing restenosis to causing late thrombosis and nouveau atherosclerosis 19. JACC Cardiovasc Imaging
  208. (1982). Organizational behavior of human umbilical vein endothelial cells 1.
  209. (2007). Outcomes associated with drug-eluting and baremetal stents: a collaborative network meta-analysis 3. Lancet
  210. (2007). Outcomes associated with drug-eluting and baremetal stents: a collaborative network meta-analysis. Lancet
  211. (2001). Paclitaxel stent coating inhibits neointimal hyperplasia at 4 weeks in a porcine model of coronary restenosis 1. Circulation
  212. (1996). Palmaz-Schatz stents coated with a NO donor reduces reocclusion when placed in a pig carotid artery for 28 days 232.
  213. (2008). PCI Audit Data. British Cardiovascular Intervention Society. Presented to Autumn Meeting
  214. (2002). Peptide blockade of HIFalpha degradation modulates cellular metabolism and angiogenesis 1.
  215. (2005). Percutaneous coronary intervention for chronic total occlusions: the Thoraxcenter experience 1992-2002. Eur Heart J
  216. (2009). Percutaneous coronary intervention in the Occluded Artery Trial: procedural success, hazard, and outcomes over 5 years 1. Am Heart J
  217. (1992). Percutaneous transluminal coronary angioplasty of chronic total occlusions. Primary success, restenosis, and long-term clinical follow-up 1. Circulation
  218. (2004). Persistent induction of HIF-1alpha and -2alpha in cardiomyocytes and stromal cells of ischemic myocardium 1. FASEB J
  219. (2002). Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2: double-blind, randomized, controlled clinical trial. Circulation
  220. (1991). Phenotypic modulations of human umbilical vein endothelial cells and human dermal fibroblasts using two angiogenic assays 1. Biol Cell
  221. (2003). phospholipase C gamma-1 is required downstream of vascular endothelial growth factor during arterial development 2. Genes Dev
  222. (1998). Phosphorylcholine-coated metallic stents in rabbit iliac and porcine coronary arteries 129. Scandinavian Cardiovascular Journal
  223. (1999). PhVEGF coated stent reduces restenosis intimal hyperplasia.
  224. (1994). Physiological assessment of augmented vascularity induced by VEGF in ischemic rabbit hindlimb 316.
  225. (2001). Physiological transport forces govern drug distribution for stent-based delivery 1006. Circulation
  226. (2002). 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. Circulation
  227. (1987). Platelet adhesion and prevention at blood-polymer interface 104. Artificial Organs
  228. (1992). Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro 94.
  229. (2000). PR39, a peptide regulator of angiogenesis 10. Nat Med
  230. (1991). Preclinical and clinical studies with recombinant human basic fibroblast growth factor 3.
  231. (2001). Predictors of improvement in left ventricular function after percutaneous revascularization of occluded coronary arteries: a report from the Total Occlusion Study of Canada (TOSCA) 7. Am Heart J
  232. (2005). Preliminary experience with the Frontrunner coronary catheter: novel device dedicated to mechanical revascularization of chronic total occlusions 5. Catheter Cardiovasc Interv
  233. (2001). Procedural outcomes and long-term survival among patients undergoing percutaneous coronary intervention of a chronic total occlusion in native coronary arteries: a 20-year experience.
  234. (2007). Prolyl hydroxylase domain 2 protein suppresses hypoxiainduced endothelial cell proliferation 4. Hypertension
  235. (2001). Protein binding alters the activity of suramin, carboxyamidotriazole, and UCN-01 in an ex vivo rat aortic ring angiogenesis assay 160. Clin Cancer Res
  236. (2001). Proteinuria in a placebo-controlled study of basic fibroblast growth factor for intermittent claudication 1. Vasc Med
  237. Purification and biological properties of vasculotropin, a new angiogenic cytokine.
  238. (2002). Rac regulates endothelial morphogenesis and capillary assembly 1.Mol Biol Cell
  239. (2006). Recent trends in the percutaneous treatment of chronic total coronary occlusions 14.
  240. (1996). Reduction in thrombotic events with heparin-coated Palmaz-Schatz stents in normal porcine coronary arteries 8. Circulation
  241. (2001). Ref Type: Abstract
  242. (1997). regulation by serum, growth factors, oncoproteins and hypoxia 1. Oncogene
  243. (2004). Regulation of angiogenesis by extracellular matrix 10. Biochim Biophys Acta
  244. (2003). Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med
  245. (2009). Regulation of oxygen homeostasis by hypoxia-inducible factor 1 1. Physiology (Bethesda )
  246. (1995). Regulation of vascular endothelial growth factor in cardiac myocytes 195. Circulation Research
  247. (1981). Regulation of wound-healing angiogenesiseffect of oxygen gradients and inspired oxygen concentration 1. Surgery
  248. (1990). Restenosis after balloon angioplasty. A practical proliferative model in porcine coronary arteries. Circulation
  249. (1992). Restenosis and the proportional neointimal response to coronary artery injury: results in a porcine model.
  250. (2009). Retrograde techniques and the impact of operator volume on percutaneous intervention for coronary chronic total occlusions an early U.S. experience 2. JACC Cardiovasc Interv
  251. (2003). Role of Angiopoietins and Tie receptor tyrosine kinases in angiogenesis and lymphangiogenesis 68. Cell Tissue Res
  252. (2008). Role of hypoxia-inducible factor 1 alpha in the integrity of articular cartilage in murine knee joints 1. Arthritis Res Ther
  253. (1988). Role of laminin and basement membrane in the morphological differentiation of human endothelial cells into capillary-like structures 3.
  254. (2009). Safety and efficacy of drugeluting and bare metal stents: comprehensive meta-analysis of randomized trials and observational studies 7. Circulation
  255. (2006). Safety of coronary sirolimuseluting stents in daily clinical practice: one-year follow-up of the e-Cypher registry. Circulation
  256. (2003). Sellke FW. Inhibition of the cardiac angiogenic response to surgical FGF-2 therapy in a Swine endothelial dysfunction model 3. Circulation
  257. (2002). Sellke FW. Longterm effects of surgical angiogenic therapy with fibroblast growth factor 2 protein 4. J Thorac Cardiovasc Surg
  258. (2005). Signalling hypoxia by HIF hydroxylases.
  259. (2001). single-blind, placebo-controlled pilot study of catheter-based myocardial gene transfer for therapeutic angiogenesis using left ventricular electromechanical mapping in patients with chronic myocardial ischemia 9. Circulation
  260. (2006). Sirolimus-eluting stents at two years: a pooled analysis of SIRIUS, ESIRIUS, and C-SIRIUS with emphasis on late revascularizations and stent thromboses.
  261. (2003). Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomised controlled trial (E-SIRIUS). Lancet
  262. (1997). Slow-release taxol coated GRII stents reduce neointimal formation in a porcine coronary in-stent restenosis model 355. Circulation Suppl I,
  263. (1988). State of the art 69. Chest
  264. (2001). Stent-based delivery of sirolimus reduces neointimal formation in a porcine coronary model 1. Circulation
  265. Stent-based rapamycin reduces neointima in a 30-day porcine coronary model 934.
  266. (2005). Stimulation of HIF-1alpha, HIF-2alpha, and VEGF by prolyl 4-hydroxylase inhibition in human lung endothelial and epithelial cells. Free Radic Biol Med
  267. (1958). Studies on erythropoiesis. V. The effect of cobalt on the production of erythropoietin. Blood
  268. (1931). Successful gene transfer to swine coronary arteries using a polymer-coated, DNA-eluting stent. XXIst Congress of the European Society of Cardiology ,
  269. Sustained stent-based delivery of paclitaxel arrests neointimal thickening and cell proliferation. Circulation 98[17S], 740I. 10-27-1998. Ref Type: Abstract
  270. (1995). Synergistic effect of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in vivo 85. Circulation
  271. (2001). Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science
  272. (2003). Targeting of mitogen-activated protein kinases and phosphatidylinositol 3 kinase inhibits hepatocyte growth factor/scatter factor-induced angiogenesis 4. Circulation
  273. (2000). The autophosphorylation of 1175-tyrosine residue on KDR/Flk-1 (VEGF receptor-2) is essential for the activation of PLC-and MAP kinase pathway for DNA synthesis in vascular endothelial cells.
  274. (2008). The importance of pre-clinical animal testing in interventional cardiology 5. Arq Bras Cardiol
  275. (1993). The isolation and culture of microvascular endothelium 8.
  276. (1995). The isolation, characterization and culture of human decidual endothelium 1. Hum Reprod
  277. (2003). The mouse aorta model: influence of genetic background and aging on bFGF- and VEGFinduced angiogenic sprouting 1. Angiogenesis
  278. (1919). The number and distribution of capillaries in muscles with calculations of the oxygen pressure head necessary for supplying the tissue.
  279. (1992). The perfusion pattern in coronary artery occlusion: comparison of exercise and adenosine.p6 5. Cathet Cardiovasc Diagn
  280. (2008). The porcine restenosis model using thermal balloon injury: comparison with the model by coronary stenting 2. J Invasive Cardiol
  281. (2003). The rat aortic ring assay for in vitro study of angiogenesis 4.Methods Mol Med
  282. The receptor tyrosine kinase inhibitor SU11248 impedes endothelial cell migration, tubule formation, and blood vessel formation in vivo, but has little effect on existing tumor vessels 2.
  283. (2002). The role of the microenvironment and intercellular cross-talk in tumor angiogenesis 7. Semin Cancer Biol
  284. (2001). The vascular anatomy of the developing zebrafish: an atlas of embryonic and early larval development 2. Dev Biol
  285. (2003). The VIVA trial: Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis. Circulation
  286. (2004). Therapeutic angiogenesis and vasculogenesis for ischemic disease. Part I: angiogenic cytokines 2. Circulation
  287. (2004). Therapeutic angiogenesis in chronically ischemic porcine myocardium: comparative effects of bFGF and VEGF 4. Ann Thorac Surg
  288. (1998). Therapeutic angiogenesis with basic fibroblast growth factor: technique and early results 3. Ann Thorac Surg
  289. (2000). Therapeutic angiogenesis with recombinant fibroblast growth factor-2 improves stress and rest myocardial perfusion abnormalities in patients with severe symptomatic chronic coronary artery disease 4. Circulation
  290. (1994). Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model.
  291. (1996). Topol EJ. Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries 141. Circulation
  292. (2000). Total occlusion trial with angioplasty by using laser guidewire. The TOTAL trial 8. Eur Heart J
  293. (2003). Transcription factor Egr-1 supports FGF-dependent angiogenesis during neovascularization and tumor growth 2. Nat Med
  294. (2005). Transendocardial and transepicardial intramyocardial fibroblast growth factor-2 administration: myocardial and tissue distribution 1. Drug Metab Dispos
  295. (1999). Transmyocardial laser revascularization: experimental and clinical results 6. Can J Cardiol
  296. Transplantation of ex vivo expanded endothelial
  297. (1998). Treatment of thromboangiitis obliterans (Buerger's disease) by intramuscular gene transfer of vascular endothelial growth factor: preliminary clinical results. J Vasc Surg
  298. (2002). trial in patients with stable angina pectoris. Circulation
  299. (1979). Tumor angiogenesis activity in clonal cells transformed by bovine adenovirus type 3 2. Cancer Res
  300. (1983). Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid.
  301. (1975). Tumor-induced angiogenesis: lack of inhibition by irradiation 1.
  302. (2004). Tumor-suppressive and promoting function of transforming growth factor beta 11. Front Biosci
  303. (2000). Type IV collagen modulates angiogenesis and neovessel survival in the rat aorta model 1. In Vitro Cell Dev Biol Anim
  304. (2006). Understanding hypoxia signalling in cells--a new therapeutic opportunity? 25. Clin Med
  305. (2000). Universal GFP reporter for the study of vascular development 1. Genesis
  306. (2005). Update on therapeutic neovascularization 1. Cardiovasc Res
  307. (1999). Use of the 10-day-old chick embryo model for studying angiogenesis 35.Methods Mol Biol
  308. (2006). Usefulness of intramyocardial injection of autologous bone marrow-derived mononuclear cells in patients with severe angina pectoris and stress-induced myocardial ischemia.
  309. (1999). Vascular endothelial growth factor (VEGF) and its receptors 5. FASEB J
  310. (1998). Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions: possible pathophysiological significance of VEGF in progression of atherosclerosis 171. Circulation
  311. (1996). Vascular endothelial growth factor administration in chronic myocardial ischemia.
  312. (1992). Vascular endothelial growth factor induces interstitial collagenase expression in human endothelial cells 945.
  313. (1992). Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo 12. Nature
  314. (2006). Vascular-specific quantification in an in vivo Matrigel chamber angiogenesis assay 3.Microvasc Res
  315. (1989). Vasculogenesis and angiogenesis: two distinct morphogenetic mechanisms establish embryonic vascular pattern 2. J Exp Zool
  316. (1998). VEGF administration in chronic myocardial ischemia in pigs 1. Cardiovasc Res
  317. (1996). VEGF improves myocardial blood flow but produces EDRFmediated hypotension in porcine hearts 1. J Surg Res
  318. (2006). versus maximum medical treatment. Gene Ther
  319. (2003). von Hippel-Lindau protein binds hyperphosphorylated large subunit of RNA polymerase II through a proline hydroxylation motif and targets it for ubiquitination 18. Proc Natl Acad Sci U S A

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.