Ezetimibe reduces plaque inflammation in a rabbit model of atherosclerosis and inhibits monocyte migration in addition to its lipid-lowering effect

Background and purpose:

Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, might also suppress inflammatory components of atherogenesis. We have studied the effects of ezetimibe on two characteristics of atherosclerotic plaques (infiltrate and fibrosis) and on expression of inflammatory genes in a rabbit model of accelerated atherosclerosis.

Experimental approach:

Femoral atherosclerosis was induced by a combination of endothelial desiccation and atherogenic diet. Animals were randomized to ezetimibe (0.6 mg·kg⁻¹·day⁻¹), simvastatin (5 mg·kg⁻¹·day⁻¹), ezetimibe plus simvastatin or no treatment, still on atherogenic diet. A control group of rabbits received normolipidemic diet.

Key results:

Rabbits fed the normolipidemic diet showed normal plasma lipid levels. Either the normolipidemic diet or drug treatment reduced the intima/media ratio (normolipidemic diet: 22%, ezetimibe: 13%, simvastatin: 27%, ezetimibe + simvastatin: 28%), compared with rabbits with atherosclerosis. Ezetimibe also decreased macrophage content and monocyte chemoattractant protein-1 expression in atherosclerotic lesions. Furthermore, ezetimibe reduced the increased activity of nuclear factor κB in peripheral blood leucocytes and plasma C-reactive protein levels in rabbits with atherosclerosis. In THP-1 cells, ezetimibe decreased monocyte chemoattractant protein-1-induced monocyte migration. Importantly, the combination of ezetimibe with simvastatin was associated with a more significant reduction in plaque monocyte/macrophage content and some proinflammatory markers than observed with each drug alone.

Conclusions and implications:

Ezetimibe had beneficial effects both on atherosclerosis progression and plaque stabilization and showed additional anti-atherogenic benefits when combined with simvastatin. Its effect on monocyte migration provides a potentially beneficial action, in addition to its effects on lipids.     

The Hong Kong Society of Rheumatology consensus recommendations for the management of gout

Clinical Rheumatology - Gout is one of the most common noncommunicable diseases in Hong Kong. Although effective treatment options are readily available, the management of gout in Hong Kong remains...     

Effect of dietary soybean and licorice on the male F344 rat: an integrated study of some parameters relevant to cancer chemoprevention.

The individual and combined effects of dietary toasted soybean meal (3.13-25%) and dietary licorice root extract (0.38-3.0%) on selected liver and intestinal enzyme levels and on clinical chemistry and histopathological parameters were evaluated on male F344 rats. All parameters were measured one and three months after the 50-day-old rats were started on the diets. By use of newly developed high-performance liquid chromatography-based analytic methods, measurable levels of daidzein (2.67 micrograms/ml) and glycyrrhetinic acid (7.87 micrograms/ml) were detected in the sera of rats on the 25% soybean and 3% licorice diets, respectively. Histopathological evaluations of organs and tissues yielded only nonsignificant strain-related changes. At all dosages, there were no significant soybean- or licorice-related anatomic lesions or hematologic changes. In the clinical biochemistry profile, soybean meal caused moderate but significant dose-dependent decreases in serum cholesterol and increases in alkaline phosphatase, blood urea nitrogen, and phosphorus, which remained within the normal range. Liver glutathione transferase, catalase, and protein kinase C showed significant inductions (up to 50%) in response to increasing doses of soybean meal and licorice extract, with evidence for only marginal interaction between the two additives. Their effects on the intestinal mucosa were not significant. Ornithine decarboxylase levels, an indicator of promotional activity, were unchanged or repressed by the additives. The favorable effects of up to 25% toasted soybean meal and 3% licorice root extract on the levels of the four enzymes, without unfavorable changes in clinical parameters, might account in part for the chemopreventive activities of these additives. These effects would be in addition to direct inhibitory effects of known components in these additives on these or other enzymes or modulation of hormone activity that is not evaluated in this study.     

Posttransplantation cyclosporine-induced lymphoproliferative disorders: clinical and radiologic manifestations

Fifteen allograft transplant recipients acquired lymphoproliferative disorders after immunosuppressive therapy with cyclosporine and steroids. Many of these lymphoproliferative disorders regressed or disappeared completely after reduction of cyclosporine dose. This disease has several aspects that distinguish it from usual posttransplantation lymphomas that occur with regimens that do not contain cyclosporine. The time course from transplantation to onset of lymphoma is relatively short, with an average of approximately 8 months. Organs show a wide spectrum of abnormalities typical of other immunosuppression-associated lymphomas, but there is unique sparing of the central nervous system. The tumor is also unique in that it responds to a decrease in the cyclosporine dose.