TY - JOUR
T1 - Modification of HDL3 by mild oxidative stress increases ATP-binding cassette transporter 1-mediated cholesterol efflux
AU - Pirillo, Angela
AU - Uboldi, Patrizia
AU - Pappalardo, Gianluca
AU - Kuhn, Hartmut
AU - Catapano, Alberico L.
PY - 2007/8/1
Y1 - 2007/8/1
N2 - Objective: Elevated levels of high-density lipoprotein (HDL) cholesterol are inversely related to the risk of cardiovascular disease. The anti-atherosclerotic function of HDL is mainly ascribed to its role in reverse cholesterol transport, and requires the integrity of HDL structure. Experimental evidence suggests that the ability of HDL to promote removal of excess cholesterol from peripheral cells is impaired upon oxidation. On the other hand, tyrosylation of HDL enhances its protective function, suggesting that not all forms of modified lipoprotein may be atherogenic. In the present study we investigated the effect of a mild oxidation of HDL3 on its function as cholesterol acceptor. Methods and results: A mild oxidative stress (induced by 15 min exposure of HDL3 to 1 μM Cu++ or to 15-lipoxygenase) caused the formation of pre-β-migrating particles. Compared to native lipoprotein, mildly modified HDL3 induced a significant ATP-binding cassette transporter 1 (ABCA1)-mediated increase of cholesterol and phospholipids efflux from J774 macrophages. This effect was abolished by an inhibitor of ABCA1-mediated lipid efflux (glyburide) and was absent in Tangier fibroblasts. Conclusions: A mild oxidative modification of HDL3 may improve its function as cholesterol acceptor, increasing ABCA1-mediated lipid efflux from macrophages, a process that may reduce foam cell formation.
AB - Objective: Elevated levels of high-density lipoprotein (HDL) cholesterol are inversely related to the risk of cardiovascular disease. The anti-atherosclerotic function of HDL is mainly ascribed to its role in reverse cholesterol transport, and requires the integrity of HDL structure. Experimental evidence suggests that the ability of HDL to promote removal of excess cholesterol from peripheral cells is impaired upon oxidation. On the other hand, tyrosylation of HDL enhances its protective function, suggesting that not all forms of modified lipoprotein may be atherogenic. In the present study we investigated the effect of a mild oxidation of HDL3 on its function as cholesterol acceptor. Methods and results: A mild oxidative stress (induced by 15 min exposure of HDL3 to 1 μM Cu++ or to 15-lipoxygenase) caused the formation of pre-β-migrating particles. Compared to native lipoprotein, mildly modified HDL3 induced a significant ATP-binding cassette transporter 1 (ABCA1)-mediated increase of cholesterol and phospholipids efflux from J774 macrophages. This effect was abolished by an inhibitor of ABCA1-mediated lipid efflux (glyburide) and was absent in Tangier fibroblasts. Conclusions: A mild oxidative modification of HDL3 may improve its function as cholesterol acceptor, increasing ABCA1-mediated lipid efflux from macrophages, a process that may reduce foam cell formation.
KW - 15-lipoxygenase
KW - ATP-binding cassette transporter 1
KW - High-density lipoprotein
KW - Oxidative stress
KW - pre-β-HDL
KW - Reverse cholesterol transport
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U2 - 10.1016/j.cardiores.2007.04.021
DO - 10.1016/j.cardiores.2007.04.021
M3 - Article
C2 - 17524375
AN - SCOPUS:34447498570
VL - 75
SP - 566
EP - 574
JO - Cardiovascular Research
JF - Cardiovascular Research
SN - 0008-6363
IS - 3
ER -