Foam cells formation by oxidized low-density lipoprotein (oxLDL) accumulation in macrophages is crucial for development of atherosclerosis. Macrophage foam cell formation is an important process in atherosclerotic plaque development.1 Atherosclerosis is initiated by dysfunction of endothelial cells at lesion-prone sites in the walls of arteries, which results in monocyte infiltration into the arterial intima. These cells differentiated into macrophages, which then internalize large amounts of oxidized low-density lipoprotein forming cholesterol-laden macrophages called “foam cells”, which in turn give rise to fatty streaks in the arterial wall. As the atherosclerotic lesion develops, the arterial wall tickness increases and oxygen diffusion into the intima is markedly reduced.2 These hypoxic regions contain large number of foam cells revealing that these cells experience hypoxia during the development of atherosclerotic lesions. Hypoxia has been demonstrated in atherosclerosis and hypoxia-inducible factor-1 (HIF-1) has been shown to promote intraplaque angiogenesis and foam cells development. Adenosine is a proangiogenic purine nucleoside released from ischemic and hypoxic tissues. In this study we found that Adenosine, under hypoxia, stimulates HIF-1α accumulation by activating adenosine receptors. This study provides the first evidence that adenosine antagonists may be useful to block important steps in the atherosclerotic plaque development ado-induced. (1) Lusis, AJ. Atherosclerosis. Nature. 2000, 407, 233-241. (2) Björnheden, T.; Levin, M.; Evaldsson, M.; Wiklund, O. Evidence of hypoxic areas within the arterial wall in vivo. Arterioscler. Thromb. Vasc. Biol. 1999, 19, 870-876.
ADENOSINE IN A HUMAN MODEL OF HYPOXIC FOAM CELLS
GESSI, Stefania;FOGLI, Eleonora;SACCHETTO, Valeria;MERIGHI, Stefania;VARANI, Katia;PRETI, Delia;BOREA, Pier Andrea
2009
Abstract
Foam cells formation by oxidized low-density lipoprotein (oxLDL) accumulation in macrophages is crucial for development of atherosclerosis. Macrophage foam cell formation is an important process in atherosclerotic plaque development.1 Atherosclerosis is initiated by dysfunction of endothelial cells at lesion-prone sites in the walls of arteries, which results in monocyte infiltration into the arterial intima. These cells differentiated into macrophages, which then internalize large amounts of oxidized low-density lipoprotein forming cholesterol-laden macrophages called “foam cells”, which in turn give rise to fatty streaks in the arterial wall. As the atherosclerotic lesion develops, the arterial wall tickness increases and oxygen diffusion into the intima is markedly reduced.2 These hypoxic regions contain large number of foam cells revealing that these cells experience hypoxia during the development of atherosclerotic lesions. Hypoxia has been demonstrated in atherosclerosis and hypoxia-inducible factor-1 (HIF-1) has been shown to promote intraplaque angiogenesis and foam cells development. Adenosine is a proangiogenic purine nucleoside released from ischemic and hypoxic tissues. In this study we found that Adenosine, under hypoxia, stimulates HIF-1α accumulation by activating adenosine receptors. This study provides the first evidence that adenosine antagonists may be useful to block important steps in the atherosclerotic plaque development ado-induced. (1) Lusis, AJ. Atherosclerosis. Nature. 2000, 407, 233-241. (2) Björnheden, T.; Levin, M.; Evaldsson, M.; Wiklund, O. Evidence of hypoxic areas within the arterial wall in vivo. Arterioscler. Thromb. Vasc. Biol. 1999, 19, 870-876.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
