Hypoxia in atherosclerosis and inflammation

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. 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. 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 plaque