Effects Of High-density Lipoprotein Research Articles

Effects of high-density lipoprotein on acetylcholine-induced coronary vasoreactivity

Recent evidence suggests that high-density lipoprotein (HDL) cholesterol has important vasoactive properties which may contribute to its beneficial effects on atherosclerotic coronary artery disease. The endothelium-dependent vasodilator acetylcholine has been used in a number of experimental studies to assess endothelial function. The relation between serum lipoproteins and acetylcholine-induced coronary vasoreactivity was investigated in patients (n = 27) undergoing elective coronary arteriography. Mean serum cholesterol, low-density lipoprotein cholesterol, HDL cholesterol and triglyceride levels were 189 ± 7 (4.84 ± 0.18 mmol/liter), 134 ± 6 (3.47 ± 0.15 mmol/liter), 41 ± 3 (1.06 ± 0.08 mmol/ liter) and 106 ± 30 mg/dl (1.20 ± 0.03 mmol/ liter), respectively. After a baseline arteriogram, acetylcholine was infused into the left main coronary artery and percent change from baseline dimension was determined in 27 angiographically smooth coronary artery segments and in 14 arterial segments with evidence of mild atherosclerotic disease. Intact vascular smooth muscle function was then confirmed in all segments by dilation to intracoronary nitroglycerin. Acetylcholine produced significant vasoconstriction of both angiographically smooth (13 ± 4%, p < 0.05 vs baseline) and diseased (19 ± 4%, p < 0.05 vs baseline) coronary segments. A positive correlation was observed between HDL cholesterol and normal acetylcholine-induced coronary vasoreactivity in both angiographically smooth (r = 0.59, p < 0.001) and diseased (r = 0.62, p < 0.02) coronary segments. No significant correlation was observed, however, between total and low-density lipoprotein cholesterol, or between total cholesterol to HDL ratio and the response of coronary artery diameter to acetylcholine infusion. These findings suggest that HDL cholesterol promotes normal endothelial cell function in both normal and atherosclerotic coronary segments. This beneficial effect may be related to a direct effect of HDL on release of endothelial-derived relaxing factor or may be secondary to its effects on endothelial cell proliferation. Thus, while HDL has important antiatherogenic properties, the clinical benefit of HDL elevation may be related, in part, to its effects on endothelial function and coronary vasoreactivity.

Effect of high-density lipoproteins on thrombin-induced platelet aggregation

Using new-developed method of aggregates radius measurement in suppression of washed human platelets, it has been shown, that HDL, in concentration of 190 ug/ml and in higher ones, totally inhibited aggregation, induced by 0.075 U/ml thrombin. For the same effect on aggregation, induced by 0.225 U/ml thrombin, HDL in concentration of 1320 ug/ml were needed.

High Density Lipoprotein Inhibits Low Density Lipoprotein Binding and Uptake by Bovine Aortic Endothelial Cells

The antiatherogenic effect of high density lipoprotein (HDL) has been attributed to either an inhibition of cholesterol uptake or to reversed cholesterol transport from peripheral cells. In order to determine whether HDL competitively blocks receptor-mediated low density lipoprotein (LDL) binding and uptake, bovine aortic endothelial cells (BAECs) were cultured in Dulbecco's modified Eagles Medium (DMEM) containing 10% LDL-free fetal bovine serum, and incubated with 125I-LDL in concentrations of either 10 or 25 micrograms protein/mL. Varying amounts of HDL (0-200 micrograms/mL) were added to the media. Following a twenty-four hour incubation period at 37 degrees C, 125I-LDL binding and uptake were measured. At the lower concentration of 125I-LDL, which represents high-affinity receptor binding, there was no significant difference in either binding or uptake within the range of HDL concentrations studied. At the higher concentration of LDL, however, there was a marked inhibition of 125I-LDL binding (p less than .006) and uptake (p less than, 001; ANOVA), which did not saturate at the highest HDL concentrations used. These data suggest that HDL does not influence high-affinity, receptor-mediated binding and uptake of LDL but that its effect is seen at a concentration of LDL representing nonspecific binding. The lack of saturation at increasing concentrations of HDL also indicates that HDL-receptor interaction is not essential for the effect.

Effects of high-density lipoproteins on storage at 4 C of fowl spermatozoa

Qualitative and quantitative characterization of lipoproteins found in seminal plasma from domestic cocks was performed after isolation by density gradient ultracentrifugation. Trigyceride-rich lipoproteins (very low, intermediate- and low density lipoproteins) were not detectable in seminal plasma. High-density lipoproteins (HDL), identified on the basis of size, chemical composition and protein moiety, were present at a concentration of 66 micrograms/ml. A fraction possibly corresponding to VHDL (very high density lipoproteins, 77% protein, 23% lipid) was also detected but appeared contaminated by a protein-rich opalescent material. Since HDL contains mostly phospholipid and cholesterol, the physiological role of these lipoproteins on the storage of fowl spermatozoa was studied. Replacing seminal plasma with a solution containing chicken HDL at physiological concentration (66 micrograms/ml) had no effect on fertilizing ability of spermatozoa stored at 4 degrees C for 24 h. However, higher concentrations of HDL (560 micrograms/ml) had deleterious effects on spermatozoa stored in vitro.

Effect of high-density lipoprotein on bovine granulosa cells: progesterone production in newly isolated cells and during cell culture

It has been proposed that changes in steroidogenesis which occur during early development of the corpus luteum may be due to increased availability of lipoproteins. Bovine follicular fluid, however, contains significant amounts of high-density lipoprotein (HDL), and granulosa cells are exposed to this lipoprotein before ovulation. To determine whether bovine granulosa cells can utilize HDL the effects of this lipoprotein on freshly isolated, non-luteinized granulosa cells and on granulosa cells undergoing luteinization in serum-free culture were examined. Cells were isolated from non-atretic, antral follicles and cultured for 12 h in 10% (v/v) lipoprotein-deficient serum to allow cell attachment. After this time cells were cultured in serum-free medium. During culture the cells underwent functional luteinization as assessed by an increase in basal progesterone output (9.6-fold in 7 days) which was associated with a marked increase in activity of cholesterol side-chain cleavage and loss of aromatase activity. Dibutyryl cyclic AMP (dbcAMP) increased basal production of progesterone about twofold but HDL alone had no effect. Addition of HDL plus dbcAMP, in contrast, caused a very marked stimulation (up to ten times) of basal steroidogenesis. This trophic effect of HDL and dbcAMP lasted at least 2 weeks. Activity of cholesterol side-chain cleavage was stimulated (threefold over basal) by dbcAMP during culture but HDL was without effect, alone or with dbcAMP. Addition of HDL (in the presence or absence of dbcAMP) to freshly isolated granulosa cells had no significant stimulatory effect on progesterone production over 12 h in six experiments, and in two of these experiments a significant inhibitory effect was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Proliferative effect of high density lipoprotein (HDL) and HDL fractions (HDL 1,2, HDL 3) on virus transformed lymphoblastoid cells

The growth-promoting activities of plasma lipoproteins (LDL, HDL, HDL 1,2, HDL 3) and total HDL apolipoproteins on a virus transformed lymphoblastoid cell line in vitro, has been compared. When maintained in lipoprotein-deficient serum-supplemented medium, these cells do not proliferate optimally. The addition of either HDL, HDL 1,2 or HDL 3 induced optimal cell proliferation as compared to the result observed in fetal calf serum-supplemented medium. The HDL 1,2 subfraction was found to be more potent than the HDL 3 subfraction in supporting cell growth. Total HDL apolipoproteins were able to support significant cell proliferation. In contrast, LDL did not promote cell growth. In serum-free conditions and in the presence of transferrin, only HDL and HDL subfractions induced cell proliferation. These results suggest that HDL and HDL subfractions could initiate B lymphoblastoid cell growth and that total HDL apolipoproteins could support a part of cell proliferation.

Prostacyclin-mediated effect of high density lipoproteins as cellular cholesterol acceptors on aortic smooth muscle cells

Low (LDL) and high (HDL) density lipoproteins stimulate prostacyclin (PGI 2) synthesis in cultured rabbit and human aortic smooth muscle cells. In this respect, the efficacy of HDL exceeded that of LDL, HDL 3 being the most effective. HDL 3 obtained from hypoalphacholesterolemic patients' serum had a lesser stimulative effect on PGI 2 synthesis as compared with HDL 3 of normolipidemic subjects. Partially purified apoprotein A-1 stimulates the metabolism of 14C-arachidonic acid accompanied with enhanced formation of prostaglandins, especially 6-keto-PGI 1α. Within a 24 h incubation in the fetal calf serum-free medium, prostaglandins I 2 and E 1 (1 × 10 −7 m) reduce the intracellular cholesterol level in human aortic smooth muscle cells by 30%. Total HDL fraction as well as HDL 3 and HDL 2b applied in combination with prostaglandins have a synergistic effect resulting in a 50% fall in intracellular cholesterol. Hypothetically, the uptake of cholesterol by HDL may include the following stages: (1) HDL interacts with the cell and activates the intracellular PGI 2 synthesis probably via apo A-1 modulatory action on arachidonic acid metabolism; (2) newly synthesized PGI 2 activates cholesteryl ester hydrolase leading to the formation of free cholesterol; (3) HDL takes up free cholesterol.

Enhanced stimulatory effect of High Density Lipoproteins (HDL) and other agonists on vascular prostacyclin production in rats fed alcohol-containing diets

Chronic administration of liquid diets containing 36% of energy as ethanol to rats increased the serum level of high density lipoproteins (HDL) by 40% and potentiated 2 to 3-fold the stimulatory effect of these lipoporteins on the production of prostacyclin by aortic rings, as compared to pair-fed controls given isocaloric carbohydrate instead of ethanol. Cross-incubations between aortic rings and HDL from either alcohol-fed or pair-fed control rats revealed two factors operating in opposite directions. On the one hand, the predominant mechanism for the potentiation was increased reactivity of the vessel to these lipoproteins. This increased reactivity was also apparent with other agonists of prostacyclin formation. On the other hand, for equal amounts of either cholesterol or protein, the HDL from alcohol-fed rats were less stimulatory than those from controls. This was associated with a smaller content of arachidonate in the HDL of alcohol-fed rats. These ethanol effects on prostacyclin, a potent vasodilator and platelet antiaggregator, may contribute to the decreased incidence of ischemic heart disease observed in moderate alcohol drinkers.

Effect of High Density Lipoproteins Modified with Dilinoleoylphosphatidylcholine Vesicles on [3H]Cholesterol Release from Macrophages

Effect of High Density Lipoproteins Modified with Dilinoleoylphosphatidylcholine Vesicles on [3H]Cholesterol Release from Macrophages

The role of arachidonic acid metabolites in cardiovascular homeostasis. Biochemical, histological and clinical cardiovascular effects of non-steroidal anti-inflammatory drugs and their interactions with cardiovascular drugs.

Derivatives of arachidonic acid may be involved in atherosclerosis and its clinical complications. There is much interest in pharmacologically manipulating the arachidonic acid cascade as a means of preventing cardiovascular disease. The development of atherosclerosis has been intensively studied and the consequences of cardiovascular or cerebrovascular vessel occlusion are too familiar. Many factors are probably involved, but the role of plasma lipoproteins and the interactions between various constituents of blood and blood vessel walls have received particular attention. The risk of cardiovascular disease associated with high plasma concentrations of the low density lipoproteins and the possible protective effects of high density lipoproteins have been well documented. Much is now known about lipoprotein biochemistry, and the importance of controlling the quantity and quality of dietary lipids has been demonstrated in epidemiological studies. In studies of patients with transient ischaemic attacks, aspirin reduced the risk of stroke and death in males, although these benefits were not as convincingly demonstrated in women. The majority of patients were given aspirin 1300 mg daily, but the optimum dosage was not properly evaluated. Administering aspirin in combination with another antiplatelet drug did not appear to offer any therapeutic advantage in these patients. Aspirin showed a positive, but non-significant trend towards reduced numbers of cardiac events, non-fatal infarcts and total mortality in patients who had experienced at least one myocardial infarction. In contrast, statistically significant beneficial effects were recorded when patients with unstable angina were administered aspirin. The risks of myocardial infarction or coronary death were reduced by 51% in 2 large studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible role of protein phosphorylation in the mitogenic effect of high density lipoproteins on cultured vascular endothelial cells.

The implication of protein phosphorylation in the mitogenic action of high density lipoproteins (HDL) on bovine vascular endothelial cells was investigated by incubating endothelial cell cultures in the presence of 32P-labeled phosphoric acid. The incorporation of 32P into proteins was measured after fractionation by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and autoradiography of the gel. In endothelial cells seeded at low density and made quiescent by serum starvation, HDL markedly and consistently enhanced the degree of phosphorylation of a Mr 27,000 protein in a time- and dose-dependent manner. Using 500 micrograms/ml HDL, 32P labeling of the 27-kDa protein was already measurable after 10 min of incubation and reached a maximum at 20-30 min. Minimal effective dose of HDL during a 30-min incubation period was in the range of 5-10 micrograms/ml. While the apolipoprotein moiety of HDL was able to mimic the effect of total HDL, the lipid part of HDL was not. Furthermore, fibroblast growth factor appeared to potentiate the effect of HDL on 27-kDa protein phosphorylation, in agreement with the synergism observed between fibroblast growth factor and HDL on endothelial cell proliferation. Two activators of protein kinase C, 12-O-tetradecanoylphorbol 13-acetate and 1-oleoyl-2-acetylglycerol also induced the phosphorylation of the 27-kDa protein. These results suggest that the 27-kDa protein may be a physiological substrate for protein kinase C and that HDL could exert their mitogenic effect on endothelial cells through activation of protein kinase C and subsequent protein phosphorylation.

Effect of high-density lipoproteins with varying ratios of apolipoprotein A-I to apolipoprotein A-II on steroidogenesis by cultured rat ovary granulosa cells

Plasma high-density lipoproteins (HDL) can provide rat ovary steroidogenic tissue with cholesterol for steroid hormone production, but the mechanism of cholesterol transfer is unknown. To test the importance of apolipoprotein A-I (the major HDL apolipoprotein) in HDL-cell interactions, we examined the ability of canine-human HDL hybrids containing various proportions of canine apolipoprotein A-I and human apolipoprotein A-II to stimulate steroidogenesis by cultured rat ovary granulosa cells. We observed that as the apolipoprotein A-I to apolipoprotein A-II ratio decreased, the ability of the hybrid particles to stimulate granulosa cell progestin (progesterone and 20α-dihydroprogesterone) production diminished. However, apolipoprotein A-I was not necessary for cholesterol transfer, since hybrids with less than 5% of their total apolipoprotein mass as apolipoprotein A-I stimulated progestin production 30% as effectively as canine HDL, which contained essentially only apolipoprotein A-I. These data indicate that the delivery of cholesterol from HDL into the rat ovary cell for steroidogenesis is not strictly dependent on the presence of a specific HDL apolipoprotein.

Effect of high density lipoproteins on permeability of rabbit aorta to low density lipoproteins

A study was made on the effect of high density lipoproteins (HDL) on the permeability of rabbit aorta to low density lipoproteins (LDL) after intravenous administration of human HDL and human [ 125I]LDL to normal and hypercholesterolemic rabbits. Evaluation of radioactivity in plasma and aorta has shown that the administration of a large dose of HDL decreased the aorta permeability rate for [ 125I]LDL on an average by 19% in normal rabbits, and by 45% in rabbits with moderate hypercholesterolemia. A historadiographic study showed that HDL also decreased the vessel wall permeability to [ 125I]LDL in normal and particularly in hypercholesterolemic animals. The suggestion was made that HDL at very high molar concentration can hamper LDL transportation through the intact endothelial layer into the intima due to the ability of HDL to compete with LDL in sites of low affinity on the surface of endothelial cells.

Effect of high-density lipoproteins on cholesterol efflux and esterification in lipid-enriched human skin fibroblasts.

The ability of high-density lipoprotein (HDL) to reduce the cholesterol content was studied in cultured fibroblasts enriched with cholesterol esters. Incubation of cholesterol-enriched cells with HDL in a final concentration of 1 g protein/l for 24 h reduced the total and esterified cholesterol content by 23% as compared with control fibroblasts incubated with albumin. Similar cholesterol efflux was obtained with HDL isolated from lecithin:cholesterol acyltransferase (LCAT)-deficient plasma. The HDL3 subfraction isolated by rate-zonal ultracentrifugation contained the major part of the cholesterol-depleting effect. HDL or HDL3 decreased CoA:cholesterol acyltransferase (ACAT) activity to 5% of the level found in control fibroblasts within 8 h of incubation. These findings suggest that ACAT activity is sensitive to a pool of intracellular cholesterol, which can be mobilized by the addition of HDL to the culture medium, and that ACAT activity is a useful measure of cholesterol efflux from cultured fibroblasts.

Inhibitory effect of high density lipoprotein subfractions on the in vitro binding of low density lipoproteins to arterial elastin

The inhibitory effects of high density lipoprotein (HDL) subfractions on the in vitro complex formation between plasma low density lipoprotein (LDL) and arterial elastin were studied. 1. (1) The inhibitory effects were significantly higher with HDL 3 than HDL 2, and with HDL-without E than HDL-with E. 2. (2) The inhibitory effect of a phospholipid complex with apoHDL 3 was higher than that with apoHDL 2. 3. (3) In contrast with the inhibitory effects, the binding abilities of HDL 2 and HDL-with E to elastin were significantly higher than those of HDL 3 and HDL-without E. 4. (4) These results suggest that the inhibitory effects of HDL subfractions are not due to competitive binding with arterial elastin.

Stability and clearance of small unilamellar liposomes studies with normal and lipoprotein-deficient mice

The effect of high density lipoproteins (HDL) on the stability and clearance of injected liposomes was investigated under conditions of abnormal lipoprotein metabolism in vivo. Small unilamellar liposomes composed of phosphatidylcholine and containing quenched carboxyfluorescein were injected intravenously or intraperitoneally into normal mice or mice previously made lipoprotein deficient with 4-aminopyrazolo[3,4 d]pyrimidine (4-APP). As evidenced from quenched carboxyfluorescein values in the blood, levels of stable liposomes in the circulation were increased and clearance rates reduced considerably in lipoprotein-deficient animals indicating increased bilayer integrity. This was confirmed by the demonstration that transfer of liposomal phosphatidylcholine to HDL, occurring in the presence of normal mouse plasma, was virtually abolished in the presence of plasma from lipoprotein deficient mice. The role of other lipoprotein species in destabilizing liposomes was also investigated. Plasma from lipoprotein-deficient mice was supplemented with increasing amounts of HDL, LDL + IDL or VLDL (to cover the physiological range of lipoprotein concentrations in mouse blood) prior to the addition of phosphatidylcholine liposomes, and incubated at 37°C. It was shown that among the lipoprotein species studied only HDL was detrimental to liposomal stability under the conditions employed. Our results indicate that use of liposomal drugs in the treatment of patients must take into account HDL fluctuations in their blood as these could after liposomal membrane permeability to the drugs and thus upset therapeutic efficiency.

Correlation between two effects of high density lipoproteins on vascular endothelial cells. The induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and the support of cellular proliferation.

Correlation between two effects of high density lipoproteins on vascular endothelial cells. The induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and the support of cellular proliferation.

Low Density Lipoprotein Binding by Cultured Human Skin Fibroblasts; the Inhibitory Effect of High-Density Lipoprotein from Patients with Liver Disease

Low Density Lipoprotein Binding by Cultured Human Skin Fibroblasts; the Inhibitory Effect of High-Density Lipoprotein from Patients with Liver Disease

Elastin—lipid interaction in the arterial wall part 2. In vitro binding of lipoprotein-lipids to arterial elastin and the inhibitory effect of high density lipoproteins on the process

The mechanism of lipoprotein binding to arterial elastin, and the inhibitory effect of high density lipoprotein (HDL) on the in vitro complex formation between plasma low density lipoprotein (LDL) and elastin were studied. The binding of LDL-cholesterol, phospholipids and triacylglycerols to delipidated elastin increased progressively with time over 24 h of incubation. The results of a kinetic study on lipoprotein-cholesterol concentration in the incubation medium, suggest that the ability to bind cholesterol to elastin decreases in the following order: very low density lipoprotein (VLDL), LDL, intermediate density lipoprotein (IDL) and HDL, and that the capacities to bind to a fixed amount of elastin decrease in the order: LDL, IDL, VLDL and HDL. When a definite amount of LDL was incubated with elastin in the presence of increasing concentrations of HDL, the binding of lipids to elastin progressively decreased. On the other hand, no release of cholesterol, bound to elastin during preincubation with LDL, could be detected in additional incubations with HDL, apoHDL or apoHDL—phospholipid complex.

The effect of high-density lipoprotein on the lipolysis of triacylglycerol in vitro

The effect of high-density lipoprotein on the lipolysis of triacylglycerol <i>in vitro</i>