Complexes of low-density lipoproteins and arterial proteoglycan aggregates promote cholesteryl ester accumulation in mouse macrophages

Vijayagopal, Parakat; Srinivasan, Sathanur R.; Jones, Kathleen M.; Radhakrishnamurthy, B.; Berenson, Gerald S.

doi:10.1016/0005-2760(85)90048-7

Cited by 92 publications

(25 citation statements)

References 35 publications

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“…In addition to LDL aggregates, "associates" between lipoproteins and various connective tissue components, such as proteoglycans (43,44), collagenaseresistent debris (45), heparin-fibronectin-denaturated collagen (46), fibronectin (47), and elastin (48) have been described. All these "associates" seem to be able to induce lipid accumulation in macrophages and smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

Three Types of Naturally Occurring Modified Lipoproteins Induce Intracellular Lipid Accumulation in Human Aortic Intimal Cells — The Role of Lipoprotein Aggregation

Tertov¹,

Sobenin²,

Gabbasov³

et al. 1992

Clinical Chemistry and Laboratory Medicine

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Summary: Blood monocytes or intimal smooth muscle cells from normal aorta were incubated with low density lipoprotein (LDL) from patients with coronary atherosclerosis, or with LDL from diabetic patients, or with lipoprotein(a) (Lp(a)). In each case there was a 2-to 4-fold rise in the intracellular cholesteryl ester content. LDL from healthy subjects failed to induce intracellular lipid accumulation in these cells. LDL from patients with coronary atherosclerosis, LDL from diabetic patients, and Lp(a) form aggregates under cell culture conditions. The ability of these lipoproteins to increase the cholesteryl ester content of cultured cells is directly correlated to the degree of lipoprotein aggregation. When aggregates were removed from the lipoprotein preparations by filtration, the latter became less effective in promoting intracellular lipid accumulation. Incubation of cells with lipoprotein aggregates, isolated by gel filtration, induced a 3-to 5-fold elevation of the cellular cholesteryl ester content.These results suggest that LDL from artherosclerotic patients, or LDL from diabetic patients, or Lp(a) have a tendency to form aggregates and that these aggregates are avidly taken up by intimal smooth muscle cells followed by lipid accumulation. This aggregation tendency may play a role in atherogenesis. Introduction. . . -« " u cations in vitro form aggregates under cell culture The accumulation of cholesteryl esters in intimal conditions (11). The degree of aggregation of modified smooth muscle cells is one of the earliest manifesta-LDL is correlated with their ability to increase the tionsof atherosclerosis. Despite intensive investigative intracellular cholesterol ester content. Removal of work, the molecular mechanisms underlying lipid dep-these aggregates from preparations of modified LDL osition within the cells still remain unknown. Native resulted in a marked suppression of lipid accumula-LDL properly isolated from healthy subjects fails to tion in cultured cells. These findings demonstrate that induce intracellular lipid accumulation in cultured the ability of in vitro modified LDL to promote incells (1 -3), while incubation of cells with LDL chem-tracellular lipid deposition depends largely on its agically modified by acetylation, methylation, glyc-gregation. Several types of modified LDL have been ation, oxidation, desialylation, or by malondialde-shown to occur in human blood. Thus Curtiss & hyde, glutaraldehyde or 4-hydroxynonenal treatment Witztum (12) demonstrated the presence of glycresults in deposition of lipid within the cells (1,3, ated LDL in the circulation of hyperglycaemic dia-4 -10). We recently reported that LDL after modifi-betic patients, and recently it was shown that LDL

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Section: Discussionmentioning

confidence: 99%

Three Types of Naturally Occurring Modified Lipoproteins Induce Intracellular Lipid Accumulation in Human Aortic Intimal Cells — The Role of Lipoprotein Aggregation

Tertov¹,

Sobenin²,

Gabbasov³

et al. 1992

Clinical Chemistry and Laboratory Medicine

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“…After 48 hours at 37°C, the cells were washed, fixed, and stained with oil red O as previously described. 15 The cells were photographed with an Olympus photomicroscope.…”

Section: Morphological Studiesmentioning

confidence: 99%

“…The mouse cells do not increase their intracellular content of unesterified cholesterol when they are incubated with LDLproteoglycan complexes formed in vitro. 15 Several studies have reported that lipid peroxidation of LDL by chemical or biologic processes leads to its increased uptake by macrophages. ever, in the current study excessive peroxidation of the lipoprotein-proteoglycan complexes that led to their increased uptake by macrophages and consequently cause enhanced synthesis of cholesteryl ester did not occur during the postmortem time interval.…”

mentioning

confidence: 99%

Lipoprotein-proteoglycan complexes from atherosclerotic lesions promote cholesteryl ester accumulation in human monocytes/macrophages.

Vijayagopal

Srinivasan

Radhakrishnamurthy

et al. 1992

Arterioscler Thromb

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Lipoprotein-proteoglycan complexes from human atherosclerotic lesions were studied to determine their ability to stimulate cholesteryl ester accumulation in human monocytes/macrophages. Complexes containing apolipoprotein (apo) B lipoproteins and proteoglycans were extracted from fatty streaks and fibrous plaque lesions of human aortas by extraction with 0.15 M NaCl. Fractionation of the complex with Bio-Gel A-50m yielded a single fraction from fatty streaks and two fractions from fibrous plaques. The complexes were further purified by antl-apo B affinity chromatography and analyzed for apolipoproteins, lipids, and glycosaminoglycans. Apo B was the only apolipoprotein present in the complexes. Although the complexes from fatty streaks and fibrous plaques contained varying proportions of hyaluronic acid, chondroitin 6-sulfate, and dermatan sulfate, heparin was present in only the fibrous plaque complexes. All three lipoprotein-proteogtycan complexes increased the rate of incorporation of [ M C]oleate into cholesteryl [ 14 C]oleate and stimulated cholesteryl ester accumulation in monocytes/macrophages. However, the complexes from fibrous plaques were more potent than those from fatty streaks in this regard. Cholesteryl ester synthesis that is mediated by the uptake of the complexes was dose dependent and showed apparent saturation, suggesting that cell surface binding may be required. Chloroquine, a lysosomotropic agent, inhibited cholesteryl ester synthesis that is induced by the complexes, indicating that lysosomal hydrolysis was essential. Cholesteryl ester synthesis that is mediated by the complexes was inhibited 70-79% by polyinosinic acid. Furthermore, excess unlabeled fibrous plaque complexes significantly inhibited the binding and interaalization of in vitro In vitro, low density lipoprotein (LDL) does not induce cholesteryl ester accumulation in macrophages from different sources, including human

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“…Salisbury et al 248 demonstrated increased cholesterol ester synthesis when macrophages were incubated with aortic proteoglycan and plasma LDL. In addition, Vijayagopal et al 249 showed that LDL complexed to aortic proteoglycan-hyaluronic acid aggregate was taken up by macrophages, but degraded more rapidly than LDL complexed to proteoglycan monomer. This enhanced degradation also was accompanied by increased cholesterol ester synthesis by the macrophage.…”

Section: Lipid Metabolismmentioning

confidence: 99%

Cell biology of arterial proteoglycans.

1989

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Complexes of low-density lipoproteins and arterial proteoglycan aggregates promote cholesteryl ester accumulation in mouse macrophages

Cited by 92 publications

References 35 publications

Three Types of Naturally Occurring Modified Lipoproteins Induce Intracellular Lipid Accumulation in Human Aortic Intimal Cells — The Role of Lipoprotein Aggregation

Three Types of Naturally Occurring Modified Lipoproteins Induce Intracellular Lipid Accumulation in Human Aortic Intimal Cells — The Role of Lipoprotein Aggregation

Lipoprotein-proteoglycan complexes from atherosclerotic lesions promote cholesteryl ester accumulation in human monocytes/macrophages.

Cell biology of arterial proteoglycans.

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