PubMed · 10024941
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C R Prentice. 1998. Transient ischaemic attacks.. https://doi.org/10.1093/qjmed%2F91.11.787
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Reduction of plasma low density lipoprotein (LDL) levels is associated with a reduced risk of myocardial infarction, stroke, and death. Some of this clinical benefit may be derived from an improvement in endothelium-dependent vasodilation. In the present study, we examined the effects of LDL reduction on cyclooxygenase (COX) activity and prostacyclin (PGI2) production. Human umbilical vein endothelial cells exposed to reduced concentrations of LDL demonstrated increased PGI2 production in a dose-dependent manner (from 0.75+/-0.2 to 2.6+/-0.2 ng/mL, P<0.0001). This alteration in PGI2 production did not result from LDL-induced changes in PGI2 synthase expression. However, selective inhibition of COX-2, but not COX-1, blocked PGI2 production under low cholesterol conditions. Addition of exogenous cholesterol induces dose-dependent reductions in endothelial COX-2 expression as measured by reverse transcription-polymerase chain reaction and by Western blotting. Pretreatment of cells with actinomycin D, a transcription inhibitor, reduced COX-2-derived PGI2 production by 45.9% (from 0.55+/-0.09 to 0.25+/-0.08 ng/mL). Taken together, these observations indicate that endothelial PGI2 production is regulated by cholesterol at the transcriptional level and that cholesterol-sensitive transcriptional pathways that regulate COX-2 expression are present in vascular tissue.
Platelet-agonist interaction results in aggregatory and secretory responses. While the activation of glycoprotein (GP) IIb/IIIa plays an essential role in platelet aggregation, its role in granule secretion is not clear. The present study was performed to examine the effect of 3-[[[[1-[4-(aminoiminomethyl) phenyl]-2-oxo-3S-pyrrolidinyl]amino]carbonyl]amino]-propanoate monohydrochloride salt (SC-57101A), a GPIIb/IIIa antagonist, on platelet alpha-granule secretion responses to collagen, ADP, and thrombin receptor activating peptide (TRAP). Both SC-57101A and prostaglandin E(1) (PGE(1)) inhibited collagen-, ADP-, and TRAP-induced platelet aggregation in a concentration-dependent manner. SC-57101A inhibited the collagen- and ADP-induced release of platelet-derived growth factor (PDGF) and beta-thromboglobulin (beta-TG) from platelets, but not TRAP-induced secretion of these granule contents. On the other hand, PGE(1) inhibited the release of PDGF and beta-TG from platelets activated with all the agonists used. ADP and TRAP elicited P-selectin expression in the absence of platelet aggregation, while collagen produced no such reaction. SC-57101A only moderately inhibited P-selectin expression induced by ADP and had no inhibitory effect on that induced by TRAP. The inhibition of ADP-induced secretion of alpha-granule contents by SC-57101A was abolished when platelets were pretreated with aspirin. These results suggest that GPIIb/IIIa activation plays a minor role, if any, in alpha-granule secretion in human platelets.