Plaque neovascularization: defense mechanisms, betrayal, or a war in progress

Ann N Y Acad Sci. 2012 Apr:1254:7-17. doi: 10.1111/j.1749-6632.2012.06497.x.

Abstract

Angiogenesis is induced from sprouting of preexisting endothelial cells leading to neovascularization. Imbalance in the angiogenic and antiangiogenic mediators triggers angiogenesis, which may be physiological in the normal state or pathological in malignancy and atherosclerosis. Physiologic angiogenesis is instrumental for restoration of vessel wall normoxia and resolution inflammation, leading to atherosclerosis regression. However, pathological angiogenesis enhances disease progression, increasing macrophage infiltration and vessel wall thickness, perpetuating hypoxia and necrosis. In addition, thin-walled fragile neovessels may rupture, leading to intraplaque hemorrhage. Lipid-rich red blood cell membranes and free hemoglobin are detrimental to plaque composition, increasing inflammation, lipid core expansion, and oxidative stress. In addition, associated risk factors that include polymorphysms in the haptoglobin genotype and diabetes mellitus may modulate the features of plaque vulnerability. This review will focus on physiological and pathological angiogenesis in atherosclerosis and summarizes the current status of anti-vascular endothelial growth factor (VEGF) therapy, microvascular rarefaction, and possible statin-mediated effects in atherosclerosis neovascularization.

Publication types

  • Review

MeSH terms

  • Anticholesteremic Agents / therapeutic use
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Diabetic Angiopathies / etiology
  • Diabetic Angiopathies / pathology
  • Haptoglobins / metabolism
  • Heme Oxygenase-1 / metabolism
  • Hemoglobins / metabolism
  • Humans
  • Hypoxia / pathology
  • Hypoxia / physiopathology
  • Neovascularization, Pathologic*
  • Neovascularization, Physiologic
  • Plaque, Atherosclerotic / etiology*
  • Plaque, Atherosclerotic / pathology*
  • Plaque, Atherosclerotic / physiopathology
  • Plaque, Atherosclerotic / therapy
  • Receptors, Cell Surface / metabolism
  • Risk Factors
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Anticholesteremic Agents
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • HP protein, human
  • Haptoglobins
  • Hemoglobins
  • Receptors, Cell Surface
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • HMOX1 protein, human
  • Heme Oxygenase-1