Combating Atherosclerosis With LXRα And PPARα Agonists: Is Rational Multitargeted Polypharmacy the Future of Therapeutics in Complex Diseases?

Effects of LXRα and PPARα activation on the regulation of lipid metabolism. Note the combined decrease and increase of LDL and HDL cholesterol, respectively, and the opposing actions on triglyceride levels. The end - effect is a highly beneficial anti-atherosclerotic lipid profile with low LDL, high HDL, and normal triglyceride concentrations. ABC, ATP-binding cassette transporter; ACC, acyl coenzyme A carboxylase; apo, apolipoprotein; CETP, cholesterol ester-transfer protein; CYP7A1, cholesterol 7α-hydroxylase; FAS, fatty acid synthase; HDL, high-density lipoprotein; LDL, low-density lipoprotein; LXR, liver X receptor; PLTP, phospholipid transfer protein; PPAR, peroxisome proliferator activator receptor; SCD-1, sterol coenzyme A desaturase-1; SREBP-1c, sterol regulatory element-binding protein-1c; TG, triglyceride.