Lipoprotein Platelet Interaction: The Effect On Platelet Cholesterol Content And Platelet Function

Abstract

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.

Characterization of the Effect of Plasma Lipoproteins on Platelet Function in vitro

“…HDL was found to have the opposite effect [2][3][4][5], Our present study was undertaken to char acterize more fully the effect of the plasma lipoproteins on aggregation and release of the GFP. The latter were employed in order to study the direct effect of the lipoproteins on the platelets without the influence of other plasma constituents.…”

“…Similarly, in hypercholesterolemic patients (phenotype Ila) with raised plasma low density lipoprotein (LDL) levels, increased in vivo [18,23] and in vitro [22] platelet activation has been shown. A decreased plasma high density lipoprotein (HDL) concentration associated with a sig nificant increase in platelet aggregation has been noted in females taking oral contracep tives [9], Aviram et al [1] have demonstrated that human platelets possess receptors for plasma lipoproteins and that in vitro thrombin-in duced platelet aggregation is profoundly af fected by the presence of plasma lipoproteins [2]. Incubation of very low density lipopro teins or low density lipoprotein with gel-fil tered platelets (GFP) results in increased thrombin induced platelet aggregation and l4C-serotonin release, whereas incubation with HDL has the opposite effect [2][3][4][5].…”

Hypocholesterolemia and hypertensive intracerebral hemorrhage: any association?

“…On the other hand, Ruíz-Sandoval and coworkers found that hypocholesterolemia was more common in young patients (below the age of 20 years) with hemorrhagic stroke and in those who have been diagnosed with a cryptogenic type of intracerebral hemorrhage (24). The precise mechanism behind this increased risk of intracerebral hemorrhage in patients with hypolipidemia is unclear; a high diastolic blood pressure might work with low serum cholesterol to weaken the endothelium of intracerebral arteries or that hypocholesterolemia might result in platelet hypo-activity and dysfunction (3,25).…”

Platelet Lipoprotein Interactions

“…Binding of LDL to platelets has been found to result in an increase in platelet cholesterol. 35 ' 36 A similar increase in platelet cholesterol has resulted from incubation of platelets with cholesterol-rich lipo somes. 37 Fatty acid content of the platelet membrane quantitatively parallels that of the lipoprotein 38 and a positive correlation between platelet cholesterol con tent and plasma cholesterol concentration as well as between the cholesterol to phospholipid ratio in the platelets and LDL has been found.…”