title: Intraplaque neovascularization as a novel therapeutic target in advanced atherosclerosis.
abstract: BACKGROUND
  Atherosclerosis is a lipid-driven inflammatory process with a tremendously high mortality due to acute cardiac events. There is an emerging need for new therapies to stabilize atherosclerotic lesions. Growing evidence suggests that intraplaque (IP) neovascularisation and IP hemorrhages are important contributors to plaque instability.
  
  
  METHODS
  Neovascularization is a complex process that involves different growth factors and inflammatory mediators of which their individual significance in atherosclerosis remains poorly understood. This review discusses different aspects of IP neovascularization in atherosclerosis including the potential treatment opportunities to stabilize advanced plaques. Furthermore, we highlight the development of accurate and feasible in vivo imaging modalities for IP neovascularization to prevent acute events.
  
  
  CONCLUSIONS
  Although lack of a valuable animal model of IP neovascularization impeded the investigation of a causal and straightforward link between neovascularization and atherosclerosis, recent evidence shows that vein grafts in ApoE*3 Leiden mice as well as plaques in ApoE(-/-) Fbn1(C1039G+/-) mice are useful models for intraplaque neovessel research. Even though interference with vascular endothelial growth factor (VEGF) signalling has been widely investigated, new therapeutic opportunities have emerged. Cell metabolism, in particular glycolysis and fatty acid oxidation, appears to perform a crucial role in the development of IP neovessels and thereby serves as a promising target.
authors.affiliation: a Laboratory of Physiopharmacology , University of Antwerp , Antwerp , Belgium.
authors.forename: Bieke
authors.initials: B
authors.lastname: Van der Veken
authors.affiliation: a Laboratory of Physiopharmacology , University of Antwerp , Antwerp , Belgium.
authors.forename: Guido Ry
authors.initials: GR
authors.lastname: De Meyer
authors.affiliation: a Laboratory of Physiopharmacology , University of Antwerp , Antwerp , Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Martinet
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology; D006470:Hemorrhage / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D010084:Oxidation-Reduction; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology
chemical_list: D005227:Fatty Acids
keywords: Atherosclerosis; VEGF; animal model; cell metabolism; imaging; neoangiogenesis; neovascularization