Glucose suppresses the enhancement by free fatty acids on thrombin- stimulated production of prostacyclin in cultured aortic endothelial cells.

BACKGROUND

Prostacyclin (PGI2) is a potent vasodilator and inhibitor of platelet aggregation. It may reduce in diabetic patients to contribute to the platelet hyperaggregability and acceleration of atherosclerosis. While the major clinical manifestation of diabetes mellitus is increased blood levels of glucose, elevation of free fatty acids (FFA) levels in the circulation has also been reported.

METHODS

Cultured rat aortic endothelial cells were treated with media containing high concentration of FFA (oleic acid 0.5 mM, palmitic acid 0.25 mM, linoleic acid 0.25 mM, stearic acid 0.06 mM, arachidonic acid 0.04 mM, total 1.1 mM, and the molar ratio of FFA/albumin < 2), glucose (22 mM) or both. Then the PGI2 release was studied by measuring 6-keto-PGF1alpha in the media.

RESULTS

We found that high concentration of FFA increased the PGI2 production at basal (1.227 +/- 0.031 vs 0.762 +/- 0.028 ng/mg protein, n = 6, p = 0.002) and when stimulated by 0.5 unit/ml of thrombin (2.708 +/- 0.115 vs 1.337 +/- 0.225 ng/mg protein, n = 6, p = 0.002). Two-day treatment with high-glucose did not affect PGI2 production. However, in the presence of high-glucose, the enhancement by high FFA of thrombin stimulated PGI2 production disappeared (high-glucose 1.461 +/- 0.312 ng/mg, normal-glucose 2.708 +/- 0.115 ng/mg, n = 6, p = 0.002).

CONCLUSIONS

The interaction between glucose and FFA can reduce PGI2 production in thrombin-stimulated state. Our findings further support their role in the pathogenesis of platelet hyperaggregability and acceleration of atherosclerosis in diabetes.