In vitro oxidised HDL is recognised by the scavenger receptor of macrophages: implications for its protective role in vivo

Ville, A.E. La; Solà, Rosa; Balanya, J.; Turner, Peter R.; Masana, Luís

doi:10.1016/0021-9150(94)90048-5

Cited by 43 publications

(14 citation statements)

References 35 publications

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“…It has been reported that modifications of HDL particles affect their functionality by either changing their specificity towards receptors 29,30 or their ability to promote efflux. Thus Francis et al have shown that oxidative tyrosylation of HDL promotes formation of AI-AII heterodimers that can enhace efflux 31,32.…”

Section: Discussionmentioning

confidence: 99%

The Ability to Promote Efflux Via ABCA1 Determines the Capacity of Serum Specimens With Similar High-Density Lipoprotein Cholesterol to Remove Cholesterol From Macrophages

Llera-Moya

Drazul-Schrader

Asztalos

et al. 2010

ATVB

355

322

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Objective-We measured efflux from macrophages to apolipoprotein B-depleted serum from 263 specimens and found instances in which serum having similar high-density lipoprotein cholesterol (HDL-C) differed in their efflux capacity. Thus, we wanted to elucidate why efflux capacity could be independent of total HDL-C or apolipoprotein A-I (apoA-I). Methods and Results-To understand why sera with similar HDL-C or apoA-I could differ in total efflux capacity, we assessed their ability to promote efflux via the pathways expressed in cAMP-treated J774 macrophages. Briefly, macrophages were preincubated with probucol to block ABCA1, with BLT-1 to block SR-BI, and with both inhibitors to measure residual efflux. ABCG1 efflux was measured with transfected BHK-1 cells. We used apolipoprotein B-depleted serum from specimens with similar HDL-C values at the 25 th and 75 th percentiles. Specimens in each group were classified as having high or low efflux based on total efflux being above or below the group average. We found that independently of HDL-C, sera with higher efflux capacity had a significant increase in ABCA1-mediated efflux, which was significantly correlated to the concentration of pre␤-1 HDL. The same result was obtained when these sera were similarly analyzed based on similar apoA-I. Key Words: ABCA1 Ⅲ apolipoprotein A-I Ⅲ cholesterol efflux Ⅲ high-density lipoprotein cholesterol Ⅲ macrophages E pidemiological and interventional studies 1-4 demonstrate an inverse relationship between high-density lipoprotein cholesterol (HDL-C) levels and coronary heart disease, which is an observation also supported by animal studies. 5 Thus, high HDL-C levels are thought to independently reduce coronary heart disease risk. Although HDL has been shown to have both antioxidant and antiinflammatory properties, 6 its beneficial antiatherogenic effect is likely attributable to its central role in reverse cholesterol transport, ie, the transport of cholesterol from peripheral tissues to the liver for excretion to reduce its accumulation in tissue cells such as vessel wall macrophages. 7 Because both HDL metabolism and cholesterol transport are complex processes, it has been difficult to obtain in vivo evidence that modulating HDL levels can affect removal of cholesterol from macrophage foam cells in the vessel wall and reduce atherosclerotic lesions. Overexpression of apolipoprotein (apo) A-I in mice can reduce progression of atherosclerotic lesions, 8 and infusion of apoA-I/phospholipid complexes in humans promotes lesion regression and increases fecal excretion of bile acids. 9 However, results of studies in subjects with monogenic disorders of HDL metabolism 10,11 and post hoc analyses of epidemiological studies raise questions regarding the mechanism underlying the association between HDL-C levels and coronary heart disease. 12 We recently demonstrated that in healthy individuals having a wide range of HDL-C and apoA-I levels, the capacity of serum HDL to promote cholesterol efflux from macrophages in vitro is negatively correla...

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Section: Discussionmentioning

confidence: 99%

The Ability to Promote Efflux Via ABCA1 Determines the Capacity of Serum Specimens With Similar High-Density Lipoprotein Cholesterol to Remove Cholesterol From Macrophages

Llera-Moya

Drazul-Schrader

Asztalos

et al. 2010

ATVB

355

322

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“…Lipoproteins were oxidized for 12 h at room temperature (rt) in 0.15 M NaCl supplemented with 7.5 µM Cu 2+ [32]. The oxidation procedure was terminated by dialysing the lipoproteins against TBE (4°C; pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

Comparison of the binding and endocytosis of high-density lipoprotein from healthy (HDL) and inflamed (HDL SAA ) donors by murine macrophages of four different mouse strains

Röcken

Kisilevsky

1998

Virchows Archiv

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Serum amyloid A (SAA) is a plasma acute phase protein and the precursor of the AA-fibril protein deposited in AA-amyloidosis. SAA is bound mainly to high-density lipoproteins (HDL(SAA)). Previous investigations have demonstrated that peritoneal macrophages (mO) from mice are capable of binding and endocytosing HDL(SAA). This observation may indicate a pathway by which SAA enters the mO and where its intracellular metabolism may be followed by degradation and/or amyloidogenesis. Since binding and internalization defects of lipoproteins may be associated with different diseases, it is possible that mouse strain susceptibility to amyloidosis is associated with qualitative differences in the binding and internalization of HDL(SAA). To test this hypothesis a series of binding and internalization experiments was performed in vitro with mO from four different mouse strains, CD-1, A/J, C57BL/6J and C3H/HeJ, which differ in their susceptibility to AA-amyloidosis. Using colloidal gold-labelled lipoproteins, it was evident by light and electron microscopy that mO from all four mouse strains are capable of binding and internalizing HDL (without SAA) and HDL(SAA). HDL and HDL(SAA) were found in such compartments of the receptor-mediated pathway as coated pits, coated vesicles, endosomes and multivesicular bodies and in lipid droplets; no qualitative differences were observed. Therefore, it is unlikely that a defect in binding and uptake of HDL(SAA) is related to the different susceptibilities of these mouse strains to develop AA-amyloidosis. However, the results do not exclude the possibility that differences in the intracellular processing of SAA following endocytosis of HDL(SAA) is involved in this differing susceptibility.

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“…Apo E-containing HDL that is bound to and retained by the arterial wall may be susceptible to oxidation, after which it could be taken up by macrophages and be potentially atherogenic. 30 In fact, a recent article describes the presence of oxidized HDL in atheromatous plaques. 31 On the other hand, apo E within the ECM and artery wall could be atheroprotective.…”

Section: Olin-lewis Et Almentioning

confidence: 99%

Apolipoprotein E Mediates the Retention of High-Density Lipoproteins by Mouse Carotid Arteries and Cultured Arterial Smooth Muscle Cell Extracellular Matrices

Olin-Lewis

Benton

Rutledge

et al. 2002

Circulation Research

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Abstract-Lipoprotein retention in the vascular extracellular matrix (ECM) plays a critical role in atherogenesis. Previous studies demonstrated the presence of apo A-I and E in atherosclerotic lesions, suggesting that HDL may be trapped by the artery wall. We sought to determine mechanisms by which HDL could be bound and retained by the arterial wall, and whether apo E was a principal determinant of this binding. We evaluated in situ accumulation of fluorescently labeled DiI-human HDLϮapo E in perfused carotid arteries from apo E-null mice. Apo E was important in mediating HDL binding to the vascular wall, with a 48Ϯ16% increase in accumulation of DiI-labeled apo E-containing HDL (HDL 3 ϩE) compared with DiI-apo E-free HDL (HDL 3 ϪE) (Pϭ0.003). To investigate possible mechanisms responsible for retention, we assessed binding of unlabeled HDL 3 ϪE and HDL 3 ϩE to ECM generated by cultured arterial smooth muscle cells. Similar to the in situ carotid artery data, HDL 3 ϩE bound better to the ECM than did HDL 3 ϪE (3-fold lower K a and 3.5-fold higher B max for HDL 3 ϩE versus HDL 3 ϪE). These differences were eliminated after either neutralization of arginine residues on apo E or digestion of matrix with chondroitin ABC lyase, suggesting that chondroitin and/or dermatan sulfate proteoglycans were responsible for apo E-mediated increased binding. These findings demonstrate that HDL can bind to both intact murine carotid arteries and smooth muscle cell-derived ECM, and that apo E is a principal determinant in mediating the ability of HDL to be trapped and retained via its interaction with ECM proteoglycans. Key Words: apolipoprotein E Ⅲ high-density lipoproteins Ⅲ extracellular matrix Ⅲ artery wall Ⅲ proteoglycan T he retention of lipoproteins in the arterial extracellular matrix (ECM) is a critical step in atherogenesis. 1-3 Apolipoproteins (apo) B and E, found on triglyceride-rich, atherogenic lipoproteins, have been found extensively in atherosclerotic lesions, often associated with ECM proteoglycans. 4 However, immunohistochemical studies show that apo A-I, which is the primary apolipoprotein on HDL, is present in human atherosclerotic lesions as well. 4 -7 Further, apo A-I and E were found to colocalize with biglycan, 4 a major arterial extracellular proteoglycan, suggesting that HDL can be trapped by ECM proteoglycans. We also have shown that apo E-containing HDL (HDLϩE) binds to purified matrix proteoglycans in vitro, whereas apo E-free HDL (HDLϪE) does not bind. 4,8 Because HDLϪE contains a large amount of apo A-I, this suggests that apo A-I itself does not bind to proteoglycans. This hypothesis is supported by reports that mammalian apo A-I does not contain heparin binding domains. 9 Therefore, these data indicate that apo E may play an important role in the retention of HDL by ECM proteoglycans.Because the artery wall contains ECM components in addition to proteoglycans, we conducted studies to evaluate the hypothesis that the presence of apo E on HDL could affect its retention by the intact vascular ECM. ...

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In vitro oxidised HDL is recognised by the scavenger receptor of macrophages: implications for its protective role in vivo

Cited by 43 publications

References 35 publications

The Ability to Promote Efflux Via ABCA1 Determines the Capacity of Serum Specimens With Similar High-Density Lipoprotein Cholesterol to Remove Cholesterol From Macrophages

The Ability to Promote Efflux Via ABCA1 Determines the Capacity of Serum Specimens With Similar High-Density Lipoprotein Cholesterol to Remove Cholesterol From Macrophages

Comparison of the binding and endocytosis of high-density lipoprotein from healthy (HDL) and inflamed (HDL SAA ) donors by murine macrophages of four different mouse strains

Apolipoprotein E Mediates the Retention of High-Density Lipoproteins by Mouse Carotid Arteries and Cultured Arterial Smooth Muscle Cell Extracellular Matrices

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