[New understanding of the onset of atherosclerosis--angiogenesis and hypoxia play a crucial role].
Clinical signs of atherosclerosis, such as heart attack and stroke, are often caused by rupture of the cap of an atherosclerotic plaque, with thrombus formation as a consequence. The risk of rupture depends on the formation of microvessels (angiogenesis) in the plaque. The fragility of the microvascular endothelium causes hyperpermeability, which leads to intraplaque haemorrhage. Angiogenesis is stimulated by hypoxia, oxidative stress and the production of hypoxia-inducible transcription factors. Hypoxia is primarily caused by increased oxygen consumption of inflammatory cells, while plaque thickness, which reduces oxygen diffusion, contributes to a limited extent. A vicious circle of hypoxia, (incomplete) angiogenesis and inflammation occurs deep in the plaque, which enhances plaque growth and the risk of plaque rupture. By non-invasive imaging of plaque hypoxia and angiogenesis, plaques at risk of rupture may be identified. Therapeutic interventions for plaque angiogenesis and hypoxia require further investigation.
Sluimer
Judith C
JC
Maastricht Universitair Medisch Centrum, afd. Pathologie, Maastricht, The Netherlands.
Daemen
Mat J A P
MJ
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D012307:Risk Factors
D020533:Angiogenesis Inhibitors