Appropriate management of lipids is a central component of risk reduction in patients with coronary artery disease (CAD). According to the most recent guidelines, low-density lipoprotein cholesterol (LDLC) is the principal target of lipid-lowering therapy and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the mainstay of this therapy. The actual target level of LDL lowering is being reassessed in light of recent clinical trials. Once appropriate LDL lowering has been achieved, treatment of other targets such as high-density lipoprotein cholesterol (HDLC), triglycerides, and non-HDLC should be considered. In addition to dyslipidemia, multiple observational studies suggest that inflammatory markers such as C-reactive protein (CRP) are associated with risk of cardiovascular events and that treatment with statins may lower CRP levels. However, there are insufficient data at this time supporting treatment of CRP as a principal target in CAD.
[Show abstract][Hide abstract] ABSTRACT: Fish oil (FO) is a potent anti-inflammatory and lipid-lowering agent. Because inflammation can modulate lipid metabolism and vice versa, we hypothesized that combining FO with cyclooxygenase inhibitors (COXIBs), well-known anti-inflammatory drugs, can enhance the anti-inflammatory and lipid-lowering effect of FO. LDLR (-/-) mice were fed a high-fat diet supplemented with 6% olive oil or FO for 12 wk in the presence or absence of indomethacin (Indo, 6 mg/l drinking water). FO reduced plasma total cholesterol by 30% but, in combination with Indo, exerted a greater decrease (44%). The reduction of liver cholesterol ester (CE) and triglycerides (TG) by FO (63% and 41%, respectively) was enhanced by Indo (80% in CE and 64% in TG). FO + Indo greatly increased the expression of genes modulating lipid metabolism and reduced the expression of inflammatory genes compared with control. The mRNA and/or protein expression of pregnane X receptor (PXR) and cytochrome P450 isoforms that alter inflammation and/or lipid metabolism are increased to a greater extent in mice that received FO + Indo. Moroever, the nuclear level of PXR is significantly increased in FO + Indo group. Combining FO with COXIBs may exert their beneficial effects on inflammation and lipid metabolism via PXR and cytochrome P450.
The Journal of Lipid Research 07/2012; 53(10):2186-97. DOI:10.1194/jlr.M029843 · 4.42 Impact Factor
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