Effect of high and low density lipoproteins on proliferation of cultured bovine vascular endothelial cells.

Tauber, J. P.; Cheng, J.; Gospodarowicz, Denis

doi:10.1172/jci109907

Cited by 188 publications

(80 citation statements)

References 27 publications

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“…The effects of HDL and LDL on the morphology of smooth muscle cells were similar to those reported previously by Gospodarowicz and co-workers (Gospodarowicz et al, 1981;Tauber et al, 1980Tauber et al, , 1981a. When smooth muscle cells were incubated for 24 hours in serum-free, lipoprotein-free media (M-199), the cells appeared rounded but did not detach from the plates.…”

Section: Figure 8 Effect Of Rat and Human Hdl And Their Respective Asupporting

confidence: 89%

“…Gospodarowicz et al and other investigators have reported that plasma factors, including the lipoproteins, may influence the growth characteristics and morphology of vascular smooth muscle cells grown in tissue culture (Gospodarowicz et al, 1981;Tauber et al, 1980Tauber et al, , 1981a. Figure 5 shows phase-contrast photomicrographs illustrating the effects of serumfree M-199, and serum-free M-199 containing HDL 3 , LDL, or lipoprotein-deficient serum (LPDS), on the morphology of the cultured vascular smooth muscle cells over a 24-hour incubation period.…”

Section: The Influence Of Plasma Lipoproteins On Prostaglandin Synthementioning

confidence: 99%

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Stimulation of vascular smooth muscle cell prostacyclin and prostaglandin E2 synthesis by plasma high and low density lipoproteins.

Pomerantz¹,

Tall²,

Feinmark³

et al. 1984

Circulation Research

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SUMMARY. We studied the effects of plasma high density and low density lipoproteins upon the synthesis of prostacyclin and prostaglandin E 2 by vascular smooth muscle cells. Prostaglandin synthesis was measured in 24-hour cultures by radioimmunoassay of the stable metabolites of prostacyclin, 6-keto-prostaglandin F,, t and of prostaglandin E 2 . High density lipoproteins induced dose-dependent increases in the release of 6-keto-prostaglandin F,,, and of prostaglandin E 2 from smooth muscle cells to values 14-and 50-fold above control. Incubations with low density lipoproteins at comparable cholesterol concentrations also induced dose-dependent release of 6-keto-prostaglandin Fi,, and prostaglandin E^ but to a lesser extent. Rat high density lipoprotein, which contained 2.5 times more cholesteryl arachidonate than human high density lipoproteins, stimulated 6-keto-prostaglandin Fi,, and prostaglandin E 2 release 2-to 3-fold more than human high density lipoproteins, whereas the delipidated apoproteins of high density lipoproteins had no significant effect on prostaglandin synthesis. II) with high density lipoprotein in stimulation of prostaglandin synthesis. The data indicate that both high and low density lipoproteins stimulate the synthesis of prostacyclin and prostaglandin E 2 by vascular smooth muscle cells. The results suggest that the lipoproteins provide arachidonate to a phospholipase-sensibve pool accessible to cyclooxygenase. (Circ Res 54: 554-565, 1984) PROSTACYCLIN (PGI 2 ) and prostaglandin E 2 (PGE 2 ) are vasodilator prostaglandins that are synthesized by blood vessels and vascular endothelial and smooth muscle cells grown in tissue culture (Moncada et al., 1977(Moncada et al., , 1979Weksler et al., 1977;Baenziger et al., 1979). Studies in perfused organs and in intact animals have indicated that the synthesis of PGI 2 and PGE 2 in vessels of organs such as the heart and kidneys, modulates the effects of vasoconstrictor stimuli, thus contributing to the maintenance of tissue perfusion (McGiff et al., 1970; Needleman et al., 1978;Oliver et al., 1980;Gunther and Cannon, 1980). Furthermore, Moncada and Vane have postulated that the balance between the production of thromboxane A 2 by platelets and the synthesis of PGI 2 by endothelial cells is important in the maintenance of vascular integrity (Moncada and Vane, 1979).The principal substrate for prostaglandin synthesis is arachidonate present in the phospholipids of cellular membranes; various mechanical and hormonal stimuli activate cell membrane phospholipases which liberate arachidonate, making it available to cyclooxygenase and other enzymes of the prostaglandin cascade (Ramwell et al., 1977;Whorton et al., 1982;and Hong and Deykin, 1982). However, arachidonate might also be derived from exogenous sources, and, in plasma, large amounts of arachidonic acid are present in esterified form in the phospholipids and cholesteryl esters of the plasma lipoproteins. In a previous study, we demonstrated that high density lipoproteins (HDL) markedly stim...

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Section: Figure 8 Effect Of Rat and Human Hdl And Their Respective Asupporting

confidence: 89%

Section: The Influence Of Plasma Lipoproteins On Prostaglandin Synthementioning

confidence: 99%

Stimulation of vascular smooth muscle cell prostacyclin and prostaglandin E2 synthesis by plasma high and low density lipoproteins.

Pomerantz¹,

Tall²,

Feinmark³

et al. 1984

Circulation Research

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“…The phenomenon was also mentioned by Alam et al 4 who observed death of human aortic smooth muscle cells at certain concentrations of LDL. That the phenomenon is not species-specific was indicated by the results of Tauber et al, 5 who confirmed the cytotoxicity of LDL, incubating bovine aortic endothelial cells with human LDL.…”

mentioning

confidence: 91%

Lipoprotein oxidation and lipoprotein-induced cytotoxicity.

Hessler¹,

Morel²,

Lewis³

et al. 1983

Arteriosclerosis

487

168

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The results of this study Indicate that when human VLDL or LDL Is prepared under conditions allowing oxidation, such oxidation renders the molecular complexes highly toxic to human skin flbroblasta growing In culture. The cytotoxicity can be predicted by assaying for the presence of thlobarbiturlc acld-reactlng substances on the lipoprotein. However, malondialdehyde, which reacts with thiobarblturlc acid and Is known to be Injurious to cells, was not cytotoxic In the same experimental system when dissolved In culture medium or covalently bound to non-toxic LDL. The toxic agent(s) on oxidized LDL Is(are) located In a llpld-extractable moiety. Since lipld peroxides and oxidized sterols can occur in vivo under various pathological conditions, the cytotoxicity of these llpoprotein-assoclated substances observed In vitro may be related to certain manifestations of these conditions. Under specific conditions, very low density lipoprotein (VLDL) has also been observed to be toxic to Received November 24, 1982; accepted February 14, 1983. cultured cells. Chan and Pollard 67 showed that VLDL fractions from rats in the late stage of pregnancy are toxic to tumorigenic and nontransformed cells. Gianturco et al. 8 showed decreased viability of bovine aortic endothelial cells exposed to VLDL from hypertriacylglycerolemic humans, and Arbogast et al. 9 found that porcine aortic endothelial cells died when exposed to VLDL from diabetic rat serum.In addition to the above reports of lipoprotein-related cell injury and death, there are a number of studies describing the inhibition of proliferation of various stimulated leukocyte populations by lipoproteins, principally VLDL and LDL. 10 " 14 Among these is the study by Schuh et al. 12 who found that LDL was inhibitory in stimulated lymphocyte populations only when there was evidence of LDL "autoxidation."The reports mentioned in the above paragraphs are evidence of a growing range of interests in the injurious effects of lipoproteins. Each of the above papers alludes to potential in vivo pathophysiological roles for these phenomena, since the lipoprotein concentrations involved are well within physiological limits.Our preliminary data 15 indicated that the cytotoxic phenomenon may be related to lipoprotein oxidation. The results of the present study indicate conclusively that oxidation renders LDL highly toxic to cultured skin fibroblasts in a concentration-dependent fashion. Our results also demonstrate that the toxic substance resides in the chloroform-methanol extractable fraction of the lipoprotein. Our measure of lipoprotein oxidation is in terms of the equivalents of

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“…Exposure of the cells to 25-hydroxycholestero1 resulted in changes in the biological activity of LDL. This lipoprotein, in contrast to HDL, has been shown to be cytotoxic at high concentrations for actively growing low-density cultures of vascular endothelial cells [5,6] and does not participate in vitro in the repair process of the wounded endothelium when cultures are exposed to serum-free medium. When cultures were preexposed to 25-hydroxycholesterol, LDL became as potent as Fig.…”

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confidence: 97%

Up‐Regulation in Vascular Endothelial Cells of Binding Sites of High Density Lipoppppprotein Induced by 25‐Hydroxycholesterol

Tauber

Goldminz

Gospodarowicz

1981

European Journal of Biochemistry

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Exposure of bovine vascular endothelial cell cultures to 25-hydroxycholesterol (50 -100 pg/ml) result in a 5 -10-fold increase in cell surface binding sites of high density lipoprotein (HDL). This increase in HDLbinding sites was dependent on time and temperature. After a 48-h exposure to the oxygenated sterol, a maximal increase in H D L binding could be observed, and newly induced binding sites disappeared rapidly once 25-hydroxycholesterol was removed from the medium. No increase in HDL-binding sites was observed when cells were maintained at 4 'C. In contrast, cultures maintained at 37 "C did show an increase in HDL-binding sites when exposed to 25-hydroxycholestero1. Since simultaneous exposure of the cells to 25-hydroxycholesterol and cycloheximide resulted in an inhibition of H D L binding to the cells, it is suggested that denovo synthesis of HDL-binding sites is induced by 25-hydroxycholesterol. When the abilities of HDLz and HDL3 to bind to newly synthesized HDL-binding sites were compared, HDL3 was found to bind more efficiently than HDL2. It is therefore unlikely that apoprotein E plays a major role in the binding of HDL to newly synthesized HDLbinding sites. When the properties of newly synthesized HDL-binding sites were analyzed, they were found to have a high affinity for HDL, since half-maximal binding was reached at a concentration as low as 5 pg HDL protein/nil, and were saturable. Such HDL-binding sites had a relaxed specificity, since they were capable of binding low density liprotein (LDL). However, when LDL bound to newly synthesized HDL binding sites, it was no longer internalized, as reflected by a 90% reduction of LDL degradation, and instead of being cytotoxic it became niitogenic.Previous studies on the interaction of H D L and LDL with vascular endothelial cell cultures have demonstrated the existence on the cell surface of H D L binding sites distinct from LDL high-affinity receptor sites [I]. In these studies, it was also demonstrated that LDL can compete with HDL for binding at the cell surface. This raises the possibility that LDL can directly bind to H D L binding sites [I].Studies done by Brown et al. [2-41 have shown that 25-hydroxycholesterol stimulates the formation and accumulation of cholesterol esters in human fibroblasts. Considered together with the finding that the same sterol suppresses HMG-CoA reductase activity [3,4], their data provide strong evidence that 25-hydroxycholesterol can get inside fibroblasts and will accumulate in an esterified form.In the present study, we have looked at the effect of 25-hydroxycholesterol on the interaction of H D L and LDL with vascular endothelial cells. Depending upon the experimental conditions one used, a 5-10-fold increase (up-regulation) in HDL binding sites synthesized de novo could be observed whcn cells were preexposed to 25-hydroxycholesterol. Furthermore, the newly synthesized HDL binding sites were saturable and had a high affinity for HDL. This was reflected by a 30 -50-fold increase in the binding of HDL when cells prei...

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Effect of high and low density lipoproteins on proliferation of cultured bovine vascular endothelial cells.

Cited by 188 publications

References 27 publications

Stimulation of vascular smooth muscle cell prostacyclin and prostaglandin E2 synthesis by plasma high and low density lipoproteins.

Stimulation of vascular smooth muscle cell prostacyclin and prostaglandin E2 synthesis by plasma high and low density lipoproteins.

Lipoprotein oxidation and lipoprotein-induced cytotoxicity.

Up‐Regulation in Vascular Endothelial Cells of Binding Sites of High Density Lipoppppprotein Induced by 25‐Hydroxycholesterol

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