Cardiovascular diseases remained as major cause of mortality worldwide due to atherosclerosis. The CETP is a glycoprotein, which promote the lipid transfer between plasma apolipoprotein B lipoprotein to HDL. Although CETP activity leads to decreases in HDL-cholesterol plasma levels, clinical tests using CETP inhibitors showed no benefits or increased mortality. Experimental evidence suggests that CETP also present anti-oxidant, anti-inflammatory and anti-adipogenic functions. Human CETP transgenic mice showed lower mortality rates and reduced inflammation in response to LPS toxin. In addition, a positive correlation between CETP plasma levels and survival rates of patient with sepsis was described. Regarding atherogenesis, the local oxidative stress is consider the earliest event and it is tightly associated with inflammation. The mitochondria is a relevant source of reactive oxygen species (ROS) in cells from several tissue. In LPS activated macrophages, the mitochondrial ROS generation precedes the pro-inflammatory cytokines secretion, and these cytokines contribute to vicious cycle ROS-inflammation-ROS. Considering that CETP is anti-inflammatory in acute phase situations, our hypothesis is that the CETP expression could reduce the mitochondrial ROS production and, in this way, would reduce also the inflammation signaling induced by mitochondrial ROS. Therefore, the objective of this project is to investigate whether CETP affects the mitochondrial ROS production in macrophages in the context of atherogenesis.
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