Search PubMed⌕ Search

Biomedical subjects

M Aviram

Publications and source records attributed to M Aviram.

260 records · Page 15Linked to original sources
PubMedDate not supplied

Platelet activation by plasma lipoproteins.

Enhanced platelet activity in patients with hypercholesterolemia and moderate hypertriglyceridemia can be attributed to increased LDL and VLDL and/or decreased HDL concentrations. In marked hypertriglyceridemia, where there is an accumulation of chylomicrons, platelet function is reduced. Treatment, whether by diet, medication, or plasmapheresis, that will result in a change in lipoprotein pattern is accompanied by a parallel change in platelet responsiveness. Incubation of lipoproteins with isolated platelets results in enhancement of platelet activation by LDL and VLDL and suppression of activity by HDL and chylomicrons. These findings have in vivo confirmation. They are even more pronounced and sometimes altered when the lipoproteins are derived from hyperlipidemic subjects. The effects of the lipoproteins on platelet activity appear to be dependent on lipoprotein composition and on factors such as cholesterol:protein ratio, apo C-III0:apo C-III2 ratio, apo B concentration, and triglyceride:protein ratio. The lipoproteins interact with platelets at specific receptor sites. Rapid change in platelet composition, particularly with regard to cholesterol, phospholipid, and fatty acid content, might ensue, with consequent alterations in membrane fluidity and enzyme activities and either suppression or activation of platelet function. This review has indicated that lipoproteins have a clear influence on platelet function. This interaction could be well of paramount importance in determining atherogenic risk.

Animals↗
PubMedDate not supplied

Platelet secretory products increase low density lipoprotein oxidation, enhance its uptake by macrophages, and reduce its fluidity.

Oxidized low density lipoprotein (Ox-LDL) is considered to be involved in the atherogenic process. Factors influencing the formation of Ox-LDL are thus of importance. Oxidation of LDL in a cell-free system in the presence of copper ions was significantly increased (up to 60%) by the presence of platelet-conditioned medium, (PCM) obtained from collagen-activated platelets for the duration of the oxidation period. The effect was time- and dose-dependent and was related to hydrogen peroxide and superoxide production, since PCM-induced enhanced LDL oxidation was inhibited by catalase and by superoxide dismutase, but not by protease treatments. PCM also reduced the fluidity of oxidized LDL by 45%. Upon incubation with a J-774 macrophage-like cell line, PCM-treated Ox-LDL enhanced cellular cholesteryl ester synthesis by 47% and lipoprotein degradation by 41%. Thus platelet secretory products appeared to enhance LDL oxidation through the involvement of oxidative agents. The resulting Ox-LDL demonstrated increased atherogenic properties.

Blood Platelets↗
PubMedDate not supplied

Phagocytosis of lipase-aggregated low density lipoprotein promotes macrophage foam cell formation. Sequential morphological and biochemical events.

Macrophages internalize aggregated low density lipoprotein (LDL) by LDL receptor-dependent phagocytosis. To investigate this model of foam cell formation, we have used human and mouse macrophages to characterize biochemically and morphologically the fate of ingested phospholipase C-modified low density lipoprotein (PLC-LDL). When LDL was digested with phospholipase C, it lost phospholipid and aggregated. Human monocyte-derived macrophages rapidly ingested and degraded 125I-PLC-LDL. The degraded PLC-LDL released free cholesterol, measured either as free sterol mass or by the stimulation of [14C]oleate incorporation into cellular cholesteryl ester. Esterification was blocked by chloroquine, a weak base that inhibits lysosomal degradation. Macrophages exposed to PLC-LDL exhibited a 30-fold to a 50-fold increase in esterified sterol: by light microscopy, cytoplasmic inclusions were abundant. The inclusions were stained with oil red O, indicating that they were neutral lipid droplets. By electron microscopy, mouse peritoneal macrophages incubated with PLC-LDL contained numerous membrane-bounded vacuoles and cytoplasmic inclusions that were not surrounded by a limiting membrane. Pulse-chase experiments demonstrated that vacuoles filled with particulate material appeared first. Subsequently, the macrophages exhibited vacuoles containing multivesicular bodies. Last, inclusions that were homogeneously electron-dense and that lacked a tripartite membrane accumulated in the cytoplasm of the cells. These results are consonant with the following model of foam cell formation. Cultured macrophages rapidly ingest PLC-LDL that is initially localized in phagosomes. The aggregated lipoprotein subsequently is digested in secondary lysosomes, thus releasing free cholesterol that is reesterified, forming cytoplasmic cholesteryl ester droplets lacking a tripartite membrane.

Foam Cells↗
PubMedDate not supplied

Intralipid infusion abolishes ability of human serum to cholesterol-load cultured macrophages.

Intralipid is widely used for intravenous alimentation and contains triglyceride-emulsion particles and phospholipid liposomes. After infusion, triglyceride-emulsion particles resemble chylomicron remnants and thus may be atherogenic. On the other hand, intravenous infusion of phospholipid liposomes produces regression of experimental atherosclerosis and abolishes the ability of hypercholesterolemic rabbit plasma to cholesterol-load cultured macrophage foam cells. To determine the net effect of intralipid infusion on cellular cholesterol balance, J-774 macrophages were incubated for 18 hours with human serum obtained before, during, and after a 6-hour infusion of 10% Intralipid. Compared to serum-free medium, pre-infusion serum increased cellular unesterified cholesterol by 76% and cholesteryl ester by 78%. In contrast, serum obtained after the 6-hour infusion reduced cellular unesterified cholesterol by 23% and cholesteryl ester by 15%. Serum obtained 18 hours after the end of the infusion still showed impaired cholesterol-loading ability. Mouse peritoneal macrophages incubated with these serum samples behaved similarly. Compared to pre-infusion serum, postinfusion serum inhibited cellular uptake of 125I-low density lipoprotein and 125I-very low density lipoprotein by 50% and 80%, respectively, and also enhanced the efflux of cellular cholesterol by 46%. We conclude that the ability of human serum to cause cholesterol accumulation in cultured macrophages is abolished by an infusion of Intralipid. This effect is mediated by a reduction in cholesterol uptake by the cells and by an increase in cell cholesterol efflux. If similar events occur in the arterial wall, Intralipid infusion might inhibit foam cell formation in vivo.

Animals↗
PubMedDate not supplied

Platelet-modified lipoprotein induced by thrombin: effect of whole blood and plasma.

The effect of thrombin, the platelet-activating agent, on lipids and lipoprotein patterns in humans was studied in whole blood, in platelet-rich plasma (PRP) and in washed platelet/lipoprotein systems. Upon incubation of whole blood at 37 C for 24 h and then centrifugation of the cells, the content of plasma cholesterol and triglyceride decreased. In the presence of thrombin (10 u/ml), plasma high-density lipoprotein (HDL) levels also markedly decreased. In PRP, plasma lipids and lipoproteins were reduced to a lesser extent than in platelet-poor plasma (PPP). In the presence of thrombin, plasma HDL was decreased in PRP, but not in PPP. The electrophoretic mobility of low-density lipoprotein (LDL) was increased following incubation of whole blood, PRP or PPP, but decreased in the presence of thrombin. When washed platelets were incubated with LDL or HDL for 24 h at 37 C, there was a significant increment in the lipid and protein content of the lipoprotein medium, resulting from platelet-released particles; this phenomenon was increased in the presence of thrombin and more so with LDL. LDL--but not HDL--electrophoretic mobility was increased following incubation with washed platelets, but thrombin caused a reduction in lipoprotein electrophoretic mobility. This study demonstrates that platelets affect lipid and lipoprotein patterns and this is influenced by thrombin treatment. Platelets release lipid-protein particles, which then interact with and modify the lipoprotein.

Adult↗