Elevated plasma levels of high-d. lipoprotein cholesterol (HDL-C) are atheroprotective and HDL-dependent reverse cholesterol transport has been related to this effect. HDL particles may, however, undergo modifications that affect their biol. activities. Lipoxygenases (LOs) belong to a family of lipid peroxidizing enzymes; among them, reticulocyte-type 15-lipoxygenase (15-LO-1) appears to play a pathophysiol. role in atherosclerosis, as its expression is increased in atherosclerotic plaques and it has been shown to oxidize low-d. lipoproteins to an atherogenic form. In this work we investigated the impact of in vitro 15-lipoxygenase-catalyzed modification of HDL3 on their ability to act as cholesterol acceptor and found that 15-LO-modified HDL3 were less effective in mediating cholesterol efflux from lipid-laden J774 cells. A reduced binding of 15-LO-modified HDL3 to scavenger receptor class B, type I (SR-BI), due to HDL apoproteins crosslinking, explained, at least in part, the obsd. redn. of cholesterol efflux. In addn., ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux was also reduced, as a consequence of pre-b-particles loss after HDL3 modification. These results suggest that 15-lipoxygenase might induce structural alterations of HDL3 particles that impair their capability of triggering reverse cholesterol transport.

15-Lipoxygenase-mediated modification of high-density lipoproteins impairs SR-BI- and ABCA1-dependent cholesterol efflux from macrophages / A. Pirillo, .Uboldi, H. Kuhn, A. L. Catapano. - In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS. - ISSN 1388-1981. - 1761:3(2006), pp. 292-300.

15-Lipoxygenase-mediated modification of high-density lipoproteins impairs SR-BI- and ABCA1-dependent cholesterol efflux from macrophages

A. Pirillo
Primo
;
.Uboldi
Secondo
;
A. L. Catapano
Ultimo
2006

Abstract

Elevated plasma levels of high-d. lipoprotein cholesterol (HDL-C) are atheroprotective and HDL-dependent reverse cholesterol transport has been related to this effect. HDL particles may, however, undergo modifications that affect their biol. activities. Lipoxygenases (LOs) belong to a family of lipid peroxidizing enzymes; among them, reticulocyte-type 15-lipoxygenase (15-LO-1) appears to play a pathophysiol. role in atherosclerosis, as its expression is increased in atherosclerotic plaques and it has been shown to oxidize low-d. lipoproteins to an atherogenic form. In this work we investigated the impact of in vitro 15-lipoxygenase-catalyzed modification of HDL3 on their ability to act as cholesterol acceptor and found that 15-LO-modified HDL3 were less effective in mediating cholesterol efflux from lipid-laden J774 cells. A reduced binding of 15-LO-modified HDL3 to scavenger receptor class B, type I (SR-BI), due to HDL apoproteins crosslinking, explained, at least in part, the obsd. redn. of cholesterol efflux. In addn., ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux was also reduced, as a consequence of pre-b-particles loss after HDL3 modification. These results suggest that 15-lipoxygenase might induce structural alterations of HDL3 particles that impair their capability of triggering reverse cholesterol transport.
High-density lipoprotein; 15-lipoxygenase; Reverse cholesterol transport; Scavenger receptor class B, type I; ATP-binding cassette transporter A1
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/25309
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