scholarly journals The aggregation of isolated human platelets in the presence of lipoproteins and prostacyclin

1983 ◽  
Vol 216 (1) ◽  
pp. 43-49 ◽  
Author(s):  
D G Hassall ◽  
J S Owen ◽  
K R Bruckdorfer

Addition of prostacyclin (PGI2) temporarily inhibits platelet aggregation and permits the isolation of platelets free from plasma proteins, which have the same sensitivity as those in plasma [Moncada, Radomski & Vargas (1982) Br. J. Pharmacol. 75, 165P]. By using a modification of this technique we have established that platelets isolated from normal subjects aggregate more readily in response to ADP and adrenaline when physiological concentrations of low-density lipoproteins (LDL) are present. At high LDL concentrations spontaneous aggregation occurs. High-density lipoproteins (HDL) and very-low-density lipoproteins (VLDL) had no effect on agonist-induced platelet aggregation at normal concentrations, but HDL sensitized at higher concentrations. These effects by lipoproteins are not accompanied by changes in platelet lipid content. Cyclohexanedione treatment of LDL to modify apolipoproteins appeared to abolish the sensitization effect, indicating that binding to receptors was essential for the effects of LDL. LDL, but not HDL, overcame the inhibitory effect of PGI2 on platelet aggregation, except at very high concentrations of PGI2. PGI2 raised the cyclic AMP content of isolated platelets, but LDL only partially prevented this rise. These results suggest that LDL may have a greater role in platelet aggregation than previously recognized and may also regulate effects of PGI2. These findings may be of relevance to an understanding of cardiovascular diseases.

1981 ◽  
Author(s):  
M Aviram ◽  
J G Brook

Intracellular cholesterol metabolism is regulated by membrane receptors which selectively bind plasma low density lipoproteins (LDL), the major extracellular source of cholesterol. Human platelets, unlike other cells, are unable to synthesize cholesterol, but bind LDL with specificity. We have shown that very low density lipoproteins (VLDL) and LDL, both of which contain apolipoprotein B compete with 125I-LDL for the platelet binding sites, while high density lipoproteins (HDL) is only able to compete to a limit extent and this by virtue of its apolipoprotein E content. Platelet uptake of both LDL and HDL is saturable at physiologic concentrations of these lipoproteins. The lipoproteins are internalized by the platelet but degradation occurs only to a limited extent. Incubation of LDL AND HDL with gel-filtered platelet results in significant changes in the platelet cholesterol content. IDL ( 1 mg protein/ml) increases cholesterol content by 15% whereas the same concentration of HDL causes a 5% reduction. In the presence of thrombin LDL enhances platelet aggregation by 300% whereas HDL decreases aggregation by 50%.We have thus shown that the lipoprotein platelet interaction alfects both platelet cholesterol content and also platelet aggregation. LDL and HDL have opposing effects and this again highlights their different roles in the atherogenic process.


1990 ◽  
Vol 36 (12) ◽  
pp. 2109-2113 ◽  
Author(s):  
R Siekmeier ◽  
W März ◽  
W Gross

Abstract Recently, polyanion precipitation assays for low-density lipoprotein (LDL)-cholesterol have been found to underestimate their analyte in normolipidemic samples (Siekmeier et al., Clin Chim Acta 1988;177:221-30). Therefore, accuracy, specificity, and interference by nonesterified fatty acids have been studied for three precipitants (obtained by heparin, dextran sulfate, or polyvinyl sulfate precipitation). At normal concentrations of LDL, precipitation is incomplete, whereas it is nearly quantitative at high concentrations of LDL. The polyvinyl sulfate reagent markedly responds to variations in the amount of non-LDL protein present in the precipitation mixture. In the dextran sulfate and the polyvinyl sulfate method, but not in the heparin method, the percentages of LDL precipitated notably increase as the concentration of the polyanion compound is decreased. In either assay, very-low-density lipoproteins, but not high-density lipoproteins, are significantly coprecipitated (dextran sulfate 28%, polyvinyl sulfate and heparin 66%) in a concentration-independent fashion. Increased concentrations of nonesterified fatty acids markedly interfere with the dextran sulfate and polyvinyl sulfate assay, but do not much affect results with the heparin reagent.


1999 ◽  
Vol 77 (2) ◽  
pp. 157-163 ◽  
Author(s):  
Louise Brissette ◽  
Marie-Claude Charest ◽  
Louise Falstrault ◽  
Julie Lafond ◽  
David Rhainds ◽  
...  

Selective uptake of cholesteryl esters (CE) from lipoproteins by cells has been extensively studied with high density lipoproteins (HDL). It is only recently that such a mechanism has been attributed to intermediate and low density lipoproteins (IDL and LDL). Here, we compare the association of proteins and CE from very low density lipoproteins (VLDL), IDL, LDL and HDL3 to HepG2 cells. These lipoproteins were either labelled in proteins with 125I or in CE with 3H-cholesteryl oleate. We show that, at any lipoprotein concentration, protein association to the cells is significantly smaller for IDL, LDL, and HDL3 than CE association, but not for VLDL. At a concentration of 20 µg lipoprotein/mL, these associations reveal CE-selective uptake in the order of 2-, 4-, and 11-fold for IDL, LDL, and HDL3, respectively. These studies reveal that LDL and HDL3 are good selective donors of CE to HepG2 cells, while IDL is a poor donor and VLDL is not a donor. A significant inverse correlation (r2 = 0.973) was found between the total lipid/protein ratios of the four classes of lipoproteins and the extent of CE-selective uptake by HepG2 cells. The fate of 3H-CE of the two best CE donors (LDL and HDL3) was followed in HepG2 cells after 3 h of incubation. Cells were shown to hydrolyze approximately 25% of the 3H-CE of both lipoproteins. However, when the cells were treated with 100 µM of chloroquine, a lysosomotropic agent, 85 and 40% of 3H-CE hydrolysis was lost for LDL and HDL3, respectively. The fate of LDL and HDL3-CE in HepG2 cells deficient in LDL-receptor was found to be the same, indicating that the portion of CE hydrolysis sensitive to chloroquine is not significantly linked to LDL-receptor activity. Thus, in HepG2 cells, the magnitude of CE-selective uptake is inversely correlated with the total lipid/protein ratios of the lipoproteins and CE-selective uptake from the two best CE donors (LDL and HDL3) appears to follow different pathways.Key words: lipoprotein, receptor, HepG2 cell, selective uptake, lipid, cholesterol, binding.


2014 ◽  
Vol 92 (3) ◽  
pp. 226-233 ◽  
Author(s):  
Amina Unis ◽  
Amany Abdelbary ◽  
Manal Hamza

Atherosclerosis is one of the most common disorders among the elderly. Depression may be associated with the development of atherosclerosis. Thus, the aim of this study is to evaluate and compare the effects of escitalopram (a selective serotonin reuptake inhibitor) with atorvastatin (a well known antihyperlipidemic drug) on high fat diet induced atherosclerosis in rats. The results of this study showed that the administration of either escitalopram or atorvastatin for 6 weeks was associated with a significant decrease in serum levels of total cholesterol, triglycerides, low density lipoproteins, very low density lipoproteins, and serum malondialdehyde, and a significant increase in high density lipoproteins when compared with the atherosclerosis model group. Histopathological examination of the aortas from the test rats revealed significant regression of atherosclerotic changes, together with a significant decrease in vascular cell adhesion molecule-1 (VCAM-1) expression in the media of both the escitalopram group and the atorvastatin group when compared with the atherosclerosis model group. This study has shown that escitalopram reduced atherosclerotic changes, thus its use as an antidepressant in elderly patients should be considered.


1984 ◽  
Vol 30 (3) ◽  
pp. 349-351 ◽  
Author(s):  
M J Bugugnani ◽  
M Koffigan ◽  
I Kora ◽  
D Ouvry ◽  
V Clavey ◽  
...  

Abstract We describe an isoelectric-focusing method for rapidly separating and quantifying apolipoprotein (apo) C-II and C-III subspecies of triglyceride-rich lipoproteins. Concentrated very-low-density lipoproteins (VLDL) or delipidated apo VLDL are focused on dry acrylamide plates, after their rehydration with ampholytes and urea. Apo C-II and apo C-III in VLDL are resolved into four major bands--C-II (pI 5.01), C-III0 (pI 5.10), C-III1 (pl 4.92), and C-III2 (pI 4.84)--at the same pI values as for purified apo C. This precise technique can be used without delipidating VLDL. The relative percentage of C apoproteins found in VLDL from plasma of normal subjects agreed with previously published data. The ratio of apo C-II to apo C-III decreased in patients with chronic renal failure or with coronary artery disease.


1998 ◽  
Vol 274 (5) ◽  
pp. L737-L749 ◽  
Author(s):  
Antonella Alberti ◽  
Franco Ravenna ◽  
Daniela Quaglino ◽  
Maurizio Luisetti ◽  
Maurizio Muraca ◽  
...  

Serum lipoproteins may enter the airways and appear in sputum (chyloptysis) when the lymphatic circulation is impaired by inflammation, neoplasia, or an abnormal proliferation of smooth muscle cells. While analyzing the bronchoalveolar lavage fluid of a patient with chyloptysis, we noticed that surfactant could not be separated from contaminating serum lipoproteins and speculated that lipoproteins might interact with surfactant components. To clarify this point we immobilized surfactant protein (SP) A on microtiter wells and incubated it with 125I-labeled very low density lipoproteins (VLDLs), low-density lipoproteins, and high-density lipoproteins. We found that SP-A binds lipoproteins. Studying in greater detail the interaction of SP-A with VLDLs, we found that the binding is time and concentration dependent; is inhibited by unlabeled lipoproteins, phospholipids, and antibodies to SP-A; is increased by Ca2+; and is unaffected by methyl α-d-mannopyranoside. Whole surfactant is a potent inhibitor of binding. Furthermore, we found that SP-A increases the degradation of VLDLs by alveolar macrophages and favors the association of VLDLs with alveolar surfactant. We conclude that SP-A influences the disposal of serum lipoproteins entering the airways and speculate that binding to alveolar surfactant might represent an important step in the interaction between exogenous substances and the lung.


1978 ◽  
Vol 176 (1) ◽  
pp. 169-174 ◽  
Author(s):  
P Thomopoulos ◽  
M Berthelier ◽  
D Lagrange ◽  
M J Chapman ◽  
M H Laudat

The effect of human plasma lipoproteins on lipogenesis from glucose has been studied in isolated rat adipocytes. The very-low-density lipoproteins increased lipogenesis specifically, whereas low-density lipoproteins and high-density lipoproteins were without effect. Such stimulation could be reproduced with partially delipidated very-low-density lipoproteins. Nod-esterified fatty acids and glycerol were also without effect. Pretreatment of the adipocytes with trypsin did not alter the effect of very-low-density lipoprotein. The presence of Ca2+ was required for the full activation of lipogenesis. The synthesis of acylglycerol fatty acids and of acylglycerol glycerol were equally increased. The effect of very-low-density lipoprotein was not additive to that of insulin. It is suggested that very-low-density lipoprotein may directly stimulate lipogenesis in fat-cells, particularly in states when the lipoproteins are present at high concentration in the circulation.


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