Abstract
Statins have pleiotropic properties which are involved in inhibiting the thrombogenic response. In this study, the effects of lovastatin on two phospholipids, phosphatidylcholine and sphingomyelin, were studied in cultured endothelial cells in the presence of an oxysterol, 27-hydroxycholesterol. After the cells were cultured with 50nM of lovastatin for 60h, lovastatin was found to decrease the incorporation of [3H]choline into phosphatidylcholine and sphingomyelin, inhibited CTP: phosphocholine cytidylyltransferase (CT) activity without altering the activity of sphingomyelin synthase and neutral sphingomyelinase. And lovastatin was not found to have a direct inhibitive effect on activity of CT. Exogenous mevalonic acid or cholesterol reversed the reduction of cholesterol concentration that was caused by lovastatin, but had no significant effect on the diminished [3H]sphingomyelin by lovastatin. The increase of [3H]sphingomyelin by 27-hydroxycholesterol was not detected in the presence of lovastatin. These findings suggest that (1) lovastatin can reduce sphingomyelin content by means of inhibiting phosphatidylcholine synthesis; and (2) The decrease in sphingomyelin is not related to the diminished cholesterol concentration or mevalonate-derived intermediates. This inhibitive effect of lovastatin on sphingomyelin may benefit cellular calcification caused by sphingomyelin.
Highlights
Oxysterols, present in human serum and lesions, have been linked to the initiation and progression of atherogenesis [1,2]. 27Hydroxycholesterol, one type of oxysterols, is synthesized in the liver by CYP27A1 as the first intermediates of classic and acidic bile acid synthetic pathways [3] and by non-hepatic cells [4]
We have shown that an increased sphingomyelin caused by 27-hydroxycholesterol was significantly reversed by lovastatin
Sphingomyelin is synthesized mainly by the phosphorylcholine headgroup's being directly transferred from phosphatidylcholine to ceramide through sphingomyelin synthase
Summary
Oxysterols, present in human serum and lesions, have been linked to the initiation and progression of atherogenesis [1,2]. 27Hydroxycholesterol, one type of oxysterols, is synthesized in the liver by CYP27A1 as the first intermediates of classic and acidic bile acid synthetic pathways [3] and by non-hepatic cells [4]. It has been detected in mammalian tissues at very low concentration [5] and was enriched in pathologic structures such as atherosclerotic lesions [1,5]. Zhou et al / Biochemistry and Biophysics Reports 5 (2016) 127–133 investigating the pleiotropic effect of lovastatin [13] Our focus this time is on whether lovastatin could reduce sphingomyelin enhanced by 27-hydroxycholesterol on cultured vascular endothelial cells, which are in direct contact with toxicants in the circulation, and are involved in atherosclerotic plaque formation
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