title: Neovascularization of the atherosclerotic plaque: interplay between atherosclerotic lesion, adventitia-derived microvessels and perivascular fat.
abstract: OBJECTIVE
  Neovascularization is a prominent feature in advanced human atherosclerotic plaques. This review surveys recent evidence for and remaining uncertainties regarding a role of neovascularization in atherosclerotic plaque progression. Specific emphasis is given to hypoxia, angiogenesis inhibition, and perivascular adipose tissue (PVAT).
  
  
  RESULTS
  Immunohistochemical and imaging studies showed a strong association between hypoxia, inflammation and neovascularization, and the progression of the atherosclerotic plaque both in humans and mice. Whereas in humans, a profound invasion of microvessels from the adventitia into the plaque occurs, neovascularization in mice is found mainly (peri)adventitially. Influencing neovascularization in mice affected plaque progression, possibly by improving vessel perfusion, but supportive clinical data are not available. Whereas plaque neovascularization contributes to monocyte/macrophage accumulation in the plaque, lymphangiogenesis may facilitate egress of cells and waste products. A specific role for PVAT and its secreted factors is anticipated and wait further clinical evaluation.
  
  
  CONCLUSIONS
  Hypoxia, inflammation, and plaque neovascularization are associated with plaque progression as underpinned by recent imaging data in humans. Recent studies provide new insights into modulation of adventitia-associated angiogenesis, PVAT, and plaque development in mice, but there is still a need for detailed information on modulating human plaque vascularization in patients.
authors.affiliation: aLaboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center bDepartment of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Victor W M
authors.initials: VW
authors.lastname: van Hinsbergh
authors.forename: Etto C
authors.initials: EC
authors.lastname: Eringa
authors.forename: Mat J A P
authors.initials: MJ
authors.lastname: Daemen
mesh_terms: D052242:Adiponectin / Q000502:physiology; D000273:Adipose Tissue / Q000473:pathology; D063194:Adventitia / Q000098:blood supply* / Q000473:pathology; D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D015687:Cell Hypoxia; D006801:Humans; D055806:Microvessels / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000097:blood / Q000276:immunology / Q000473:pathology*; D010100:Oxygen / Q000097:blood; D058226:Plaque, Atherosclerotic / Q000473:pathology / Q000503:physiopathology*
chemical_list: D052242:Adiponectin; D010100:Oxygen