Vitamin E restores reduced prostacyclin synthesis in aortic endothelial cells cultured with a high concentration of glucose

Reduced prostacyclin (PGI₂) production by the vascular wall may play an important role in the pathogenesis of vascular lesions such as atherosclerosis. The present study was undertaken to evaluate the effect of vitamin E on the production of PGI₂ and other prostaglandins (prostaglandin E₂ [PGE₂], thromboxane A₂ [TXA₂], and 15-hydroxyeicosatetraenoic acid [15-HETE]) by bovine aortic endothelial cells cultured in a high concentration of glucose (300 mg/dL). Compared with endothelial cells cultured in 100 mg/dL glucose, the production of PGI₂ and other prostaglandins, except 15-HETE, was significantly reduced in cultures containing 300 mg/dL glucose when stimulated by histamine, the Ca²⁺ ionophore, A23187, or human plasma-derived serum (PDS). The addition of vitamin E to each stimulant significantly restored the production of PGI₂, PGE₂, and TXA₂, products of the cyclo-oxygenase pathway, in aortic endothelial cells cultured in 300 mg/dL glucose. This effect of vitamin E on the stimulation of prostaglandin production was generally specific for d-α-tocopherol, but not for the other vitamin E analogs tested. However, vitamin E and the stimulants had no effect on the production of 15-HETE, a product of the lipoxygenase pathway. Moreover, vitamin E alone, without stimulants, did not affect prostaglandin production in cultured bovine aortic endothelial cells. These results suggest that vitamin E may restore reduced PGI₂, PGE₂, or TXA₂ production by bovine aortic endothelial cells cultured in a high concentration of glucose. It seems likely that vitamin E may restore depressed PGI₂ production by the vascular wall in hyperglycemic conditions such as those seen in patients with diabetes mellitus.