A Review of Time Courses and Predictors of Lipid Changes with Fenofibric Acid-Statin Combination

Fibrates activate peroxisome proliferator activated receptor α and exert beneficial effects on triglycerides, high-density lipoprotein cholesterol, and low density lipoprotein subspecies. Fenofibric acid (FA) has been studied in a large number of patients with mixed dyslipidemia, combined with a low- or moderate-dose statin. The combination of FA with simvastatin, atorvastatin and rosuvastatin resulted in greater improvement of the overall lipid profile compared with the corresponding statin dose. The long-term efficacy of FA combined with low- or moderate- dose statin has been demonstrated in a wide range of patients, including patients with type 2 diabetes mellitus, metabolic syndrome, or elderly subjects. The FA and statin combination seems to be a reasonable option to further reduce cardiovascular risk in high-risk populations, although trials examining cardiovascular disease events are missing

Deleting myeloid IL-10 receptor signalling attenuates atherosclerosis in LDLR^-/-mice by altering intestinal cholesterol fluxes

International audienceInflammatory responses and cholesterol homeostasis are interconnected in atherogenesis. Interleukin (IL)-10 is an important anti-inflammatory cytokine, known to suppress atherosclerosis development. However, the specific cell types responsible for the atheroprotective effects of IL-10 remain to be defined and knowledge on the actions of IL-10 in cholesterol homeostasis is scarce. Here we investigated the functional involvement of myeloid IL-10-mediated athero-protection. To do so, bone marrow from IL-10 receptor 1 (IL-10R1) wild-type and myeloid IL-10R1-deficient mice was transplanted to lethally irradiated female LDLR-/- mice. Hereafter, mice were given a high cholesterol diet for 10 weeks after which atherosclerosis development and cholesterol metabolism were investigated. In vitro, myeloid IL-10R1 deficiency resulted in a pro-inflammatory macrophage phenotype. However, in vivo significantly reduced lesion size and severity was observed. This phenotype was associated with lower myeloid cell accumulation and more apoptosis in the lesions. Additionally, a profound reduction in plasma and liver cholesterol was observed upon myeloid IL-10R1 deficiency, which was reflected in plaque lipid content. This decreased hypercholesterolaemia was associated with lowered very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels, likely as a response to decreased intestinal cholesterol absorption. In addition, IL-10R1 deficient mice demonstrated substantially higher faecal sterol loss caused by increased non-biliary cholesterol efflux. The induction of this process was linked to impaired ACAT2-mediated esterification of liver and plasma cholesterol. Overall, myeloid cells do not contribute to IL-10-mediated atheroprotection. In addition, this study demonstrates a novel connection between IL-10-mediated inflammation and cholesterol homeostasis in atherosclerosis. These findings make us reconsider IL-10 as a beneficial influence on atherosclerosis