[Development of new antiatherosclerotic agents--ACAT inhibitors and CETP inhibitors].
Development of new antiatherosclerotic agents were reviewed focusing on ACAT inhibitors and CETP inhibitors. ACAT inhibitors enhance intracellular degradation of VLDL in hepatocytes. Cholesterol absorption in small intestine is inhibited by ACAT inhibitors. Thus, ACAT inhibitors reduce plasma cholesterol levels. In atherosclerotic lesions, ACAT inhibitors suppress foam cell formation (cholesteryl ester accumulation) in macrophages. Since ACAT inhibitors have multiple anti-atherogenic effects, they are considered future drugs controlling hypercholesterolemia and atherosclerosis. CETP inhibitors are expected to increase HDL and decrease LDL. Although the patients with CETP deficiency show high level of HDL, recent studies showed that they are not necessarily resistant to atherosclerosis. The strategy to inhibit CETP for suppressing atherosclerosis has not been established.
Miyazaki
A
A
Department of Biochemistry, Kumamoto University School of Medicine.
Horiuchi
S
S
D000818:Animals; D001053:Apolipoproteins / Q000037:antagonists & inhibitors*; D001161:Arteriosclerosis / Q000188:drug therapy*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D006801:Humans; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D001053:Apolipoproteins; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D002785:Sterol O-Acyltransferase