title: Therapeutic angiogenesis with VEGF164 for facilitation of guidewire crossing in experimental arterial chronic total occlusions.
abstract: OBJECTIVE
  Percutaneous revascularisation of chronic total occlusions (CTO) is limited by failure of guidewire crossing. Neovascularisation within the proximal CTO segment may be important for guidewire crossing and dramatically declines in CTO beyond six weeks of age. The aims of the current study were to determine whether local delivery of a pro-angiogenic growth factor increases neovascularisation in mature CTO and facilitates guidewire crossings.
  
  
  RESULTS
  CTO (n=51) were created in the femoral arteries of 44 New Zealand white rabbits using the thrombin injection model. At 12 weeks, CTO were treated with poly-lactic-glycolic-acid (PLGA) microspheres containing either bovine serum albumin (BSA) (n=15) or recombinant mouse VEGF164 (n=14), or received no intervention (controls, n=12). Contrast-enhanced magnetic resonance angiography (CEMRA) was performed prior to treatment and at three weeks post treatment. Animals were sacrificed at three weeks post treatment and arterial samples were excised for micro-computed tomography imaging (µCT) and histologic morphometric analysis. Guidewire crossing was assessed at three weeks post treatment in an additional 10 VEGF164-treated CTO. In comparison to BSA-treated and control non-intervened CTO, VEGF164-treated CTO showed a significant increase in relative blood volume index in the proximal segment of the CTO lesion as determined by CEMRA and by µCT. Histologic measurements of microvessel area were also higher in VEGF164-treated CTO. Guidewire crossing across the proximal fibrous cap was successful in eight out of 10 VEGF164-treated CTO.
  
  
  CONCLUSIONS
  Angiogenic therapy appears to be a promising strategy to improve neovascularisation and guidewire crossing rates in CTO.
authors: Schulich Heart Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, Canada.
authors: Aaron A
authors: AA
authors: Teitelbaum
authors: Xiuling
authors: X
authors: Qi
authors: Azriel B
authors: AB
authors: Osherov
authors: Ashley R
authors: AR
authors: Fraser
authors: Michelle
authors: M
authors: Ladouceur-Wodzak
authors: Nigel
authors: N
authors: Munce
authors: Beiping
authors: B
authors: Qiang
authors: Max
authors: M
authors: Weisbrod
authors: Daniel
authors: D
authors: Bierstone
authors: Ilana
authors: I
authors: Erlich
authors: John D
authors: JD
authors: Sparkes
authors: Graham A
authors: GA
authors: Wright
authors: Bradley H
authors: BH
authors: Strauss
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000601:surgery*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D057510:Endovascular Procedures / Q000295:instrumentation* / Q000379:methods*; D005263:Femoral Artery; D066298:In Vitro Techniques; D007269:Injections, Intra-Arterial; D008297:Male; D051379:Mice; D008863:Microspheres; D055806:Microvessels / Q000166:cytology / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D043925:Angiogenesis Inducing Agents; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse