Hypoxia in atherosclerosis and inflammation.
OBJECTIVE
Hypoxia triggers various cellular processes, both in physiological and pathological conditions, and has recently also been implicated in atherosclerosis. This review summarizes the recent evidence for the presence and the role of hypoxia in atherosclerosis. Additionally, it will elucidate on hypoxic signaling, which is interlinked with inflammatory signaling, and discuss recent advances in imaging of hypoxia in atherosclerosis.


RESULTS
Hypoxia is present in atherosclerotic plaques in humans and animal models, and systemic hypoxia promotes atherosclerosis. Hypoxia stimulates proatherosclerotic processes, like deficient lipid efflux, inflammation, interference with macrophage polarization and glucose metabolism. However, the molecular mechanism of hypoxia-mediated atherogenesis remains unclear. Noninvasive imaging directly targeting plaque hypoxia has been applied in animal models of atherosclerosis, but remains to be validated in humans. Meanwhile, the metabolic marker ¹⁸F-fluorodeoxyglucose, used to detect human atherosclerosis in vivo, may serve as an indirect marker of plaque hypoxia due to enhanced glucose uptake in anaerobic metabolism.


CONCLUSIONS
Recent studies underscore the proatherogenic role of hypoxia in macrophage lipid and glucose metabolism, inflammation and polarization. These studies provide new insights into the pathogenesis of atherosclerosis and unravel novel therapeutic targets and new options for noninvasive imaging of human atherosclerotic plaques.
Department of Pathology, Cardiovascular Research Institute Maastricht-CARIM, Maastricht University Medical Center, Maastricht, the Netherlands.
Elke
E
Marsch
Judith C
JC
Sluimer
Mat J A P
MJ
Daemen
D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy; D019788:Fluorodeoxyglucose F18 / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism / Q000628:therapy; D050356:Lipid Metabolism; D008264:Macrophages / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D018810:Magnetic Resonance Angiography / Q000379:methods; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011859:Radiography; D015398:Signal Transduction
D019788:Fluorodeoxyglucose F18; D005947:Glucose