fig2

Figure 2. Metabolic pathways for cholesterol (Cho) and the main acting points of lipid-lowering agents. Statin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor, and exerts lipid-lowering effects by inhibiting the synthesis of Cho in liver and pleiotropic effects such as anti-inflammation and improvement of endothelial dysfunction. Niacins modify plasma lipid levels by inhibition of lipolysis in adipose tissues. Fibrates reduce triglyceride (TG) levels and increase high-density lipoprotein (HDL) Cho (HDL-C) levels via various mechanisms including the inactivation of peroxisome proliferator activated receptor (PPAR) α, which increases the oxidation of free fatty acid (FFA) in liver and reduces the hepatic synthesis of TG and expression of lipoprotein lipase. Omega-3 polyunsaturated fatty acids (PUFAs), the major component of fish oil, are widely used as a TG-lowering therapy and have been found against oxidative stress and inflammation. Ezetimibes reduce low-density lipoprotein (LDL) Cho (LDL-C) levels by inhibition of the absorption of Cho from intestines. Cho ester (CE) transfer protein (CETP) inhibitors increase HDL-C levels by the inhibition of CETP, which promotes the net effects on the equilibration of both CE and TG among all lipoprotein particles. Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remove LDL-C from plasma by the inhibition of PCSK9, which is a hepatic protease that decreases hepatic LDL receptor (LDL-R) leading to an increase in the plasma concentration of LDL-C. CM: chylomicron; ICAM: intercellular adhesion molecule; Ox-LDL: oxidized LDL; ROS: reactive oxygen species; SMC: smooth muscle cell; TGRL: TG-rich lipoprotein; VCAM: vascular cell adhesion molecule; VLDL: very LDL; VLDL-R: VLDL receptor