SUN-560 Simvastatin Inhibits the Pro-Inflammatory and Pro-Atherogenic Effects of Cream in Obese Subjects

Our previous work has shown that the ingestion of cream induces an increase in oxidative stress and other cellular and molecular indices of inflammation and atherosclerosis and that treatment with Vytorin for 6 weeks reduced and reversed majority of the effects of cream. However, it is not clear which component of Vytorin, simvastatin or ezetimibe, is responsible for these intriguing and potent effects. Therefore, we further investigated the effects of simvastatin treatment on indices of inflammation and atherosclerosis at baseline and following intake of dairy cream. Ten obese patients with LDL >100mg/dl were given simvastatin 40mg/day for 6 weeks. Subjects were asked to ingest 33ml of cream (about 300 Calories) containing about 85% saturated fat. Fasting and post-cream intake blood samples were obtained at baseline and at 6 weeks. Total cholesterol and LDLc concentrations were lowered significantly at 6 weeks following simvastatin (p<0.05). Cream intake at 0 week induced significant increases in MNC expression of IL-1β (by 58±16%), TNF-α (by 79±19%), CD16 (by 103±32%), MMP-9 (by 68±17%), TLR-4 (by 68±12%) and TLR-2 (by 53±9%) over the baselines (p<0.05 for all). Cream intake at 0 week also induced a significant increase in IL-1β plasma concentrations by 94±18% over the baseline. Simvastatin treatment suppressed fasting levels of CD68 expression in MNC (by 38±9, p<0.05) and fasting plasma levels of IL-18 and MMP-9 (by 24±11% and 28±12%, respectively, p>0.05) compared to fasting levels at 0 week. The increase in IL-1β, TNFα, CD16 and MMP-9 expression in MNC following cream intake at end of simvastatin treatment was significantly suppressed (by 41±15%, 48±17%, 87±16% and 34±8%, respectively, p<0.05) compared to that before simvastatin treatment. In addition, there was a paradoxical suppression of the expression of TLR-2 and TLR-4 (by 30±11% and 24±9%, respectively) below baseline levels following cream at 6 weeks. Simvastatin treatment also suppressed cream induced increases in plasma IL-1β concentrations by 37±11% (p<0.05, compared to increases at 0 week). We conclude that simvastatin exerts a powerful anti-inflammatory effect and reduces expression of pro-inflammatory mediators induced by cream intake. This effect is similar in nature to that observed previously with Vytorin with some differences in the magnitude of the changes.