Intracellular mechanisms in the activation of human platelets by low-density lipoproteins

Abstract

Low-density lipoproteins (LDL) have been shown to cause aggregation of human blood platelets at concentrations above 2 g of protein/l. The secretion of the contents of platelet dense granules was detected, but not that of the lysosomes. LDL gave rise to a mobilization of [3H]arachidonic acid from phospholipids and the appearance of products of the cyclo-oxygenase pathway after only 10 s. LDL-promoted aggregation was inhibited by both aspirin and indomethacin. There was an increase in 3H-labelled diacylglycerols and the phosphorylation of 47 kDa proteins. LDL therefore shares at least some of the mechanisms of stimulus/response coupling with those of other agonists.

Interaction of LDL and platelets in ischaemic and ischaemic risk subjects

“…E mail: Ya~hika qupl;~.hotmail.com Two complimentary mechanisms responsible for platelet hyperreactivity in hypercholesteromic subjects have been proposed (5,12). One involves alterations in the lipid composition of platelet membranes, and characteristic increases in cholesterol and arachidonic acid content (12).…”

“…Low-density lipoproteins (LDL) have been reported to possess platelet activating activities such as the enhancement of platelet sensitivity to stimuli (1)(2)(3)(4) and the induction of platelet aggregation (5)(6). Oxidative modification dramatically changes the biological properties of LDL, converting them into a form that is both atherogenic and pro-thrombotic (7)(8).…”

“…LDL enhanced flbrinogen binding in response to, aggregation (4), thromboxane A z formation and serotonin secretion by thrombin (2,9); and platelet responsiveness to epinephrine and Ca z" -ionophore (1). Acting as an independent agonist, very low concentrations of LDL (10 rag/L) induced a rise in cytosolic Ca 2~ and inositol phosphate turnover (10-11), physiological concentrations induced changes in shape (0.25 g/L to 0.5 g/L) and aggregation (>0.75 g/ L) (6), and at concentrations >3 g/L, LDL triggered phosphorylation of pleckstrin, the 47-kDa substrate of protein kinase C (PKC) (5).…”

Inhibitory mechanisms of low concentrations of oxidized low-density lipoprotein on platelet aggregation

“…Endothelial cells also induce oxLDL formation, but in turn may be damaged by oxLDL [2]. LDL has been suggested to have platelet-activating properties such as decreasing the threshold for stimulation by aggregation agents and inducing platelet aggregation [6,7]. However, evidence regarding the induction of platelet activation by LDL is controversial.…”

“…Several studies have reported inhibition of agonistinduced platelet aggregation by native LDL (nLDL) [8,9]. In others, platelet-activating effects of either lower nLDL (10-50 lg/ml) [10] or higher concentrations of LDL (more than 1-2 mg/ml) have been described [6]. Furthermore, plateletactivating activity was found to reside in oxLDL rather than in nLDL [11].…”