Therapies on the horizon for cholesterol reduction.
Statins are powerful agents for the reduction of low-density lipoprotein cholesterol (LDL-C) and reduction of cardiovascular risk. Newly developed statins with increased potency, such as rosuvastatin (Crestor) and NK-104 (in earlier clinical development), are capable of achieving marked LDL-C reductions. Cholesterol-lowering agents with mechanisms of action distinct from those of the statins are in active development. These include bile transport inhibitors, such as improved bile acid-absorbing resins and specific inhibitors of the ileal Na+/bile acid cotransporter. There are also specific inhibitors of cholesterol absorption, such as ezetimibe, which may provide cholesterol lowering that is additive to that achieved with statin treatment. Another approach is to reduce cardiovascular risk by modifying atherosclerotic processes within the arterial wall, as represented by the acyl CoA:cholesterol acyltransferase (ACAT) inhibitor avasimibe; ACAT inhibitors may reduce atherosclerotic lesions by inhibiting macrophage cholesterol storage.
Brown
W V
WV
Section on Arteriosclerosis and Lipid Metabolism, Emory Clinic, Emory University School of Medicine, Atlanta, Georgia 30322, USA. wbrow01@emory.edu
D000081:Acetamides; D000085:Acetates / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002792:Cholestyramine Resin / Q000627:therapeutic use; D000069438:Ezetimibe; D005464:Fluorobenzenes / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006913:Hydroxysteroid Dehydrogenases; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008562:Membrane Glycoproteins; D011743:Pyrimidines; D000068718:Rosuvastatin Calcium; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors; D013449:Sulfonamides; D013451:Sulfonic Acids / Q000627:therapeutic use; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
D000081:Acetamides; D000085:Acetates; D000924:Anticholesteremic Agents; D001384:Azetidines; D002352:Carrier Proteins; D002792:Cholestyramine Resin; D000069438:Ezetimibe; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006913:Hydroxysteroid Dehydrogenases; D008562:Membrane Glycoproteins; D011743:Pyrimidines; D000068718:Rosuvastatin Calcium; D002785:Sterol O-Acyltransferase; D013449:Sulfonamides; D013451:Sulfonic Acids; C037643:bile acid binding proteins; C423185:avasimibe; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)