Anti-atherosclerotic activity of triacsin C, an acyl-CoA synthetase inhibitor.
As previously reported, triacsin C, a selective inhibitor of acyl-CoA synthetase, inhibited the synthesis of cholesteryl ester and triacylglycerol in mouse peritoneal macrophages, leading to a reduction of lipid droplets. Therefore, the in vivo efficacy was studied. Low-density lipoprotein receptor-knockout (LDLR-/-) mice were fed a high cholesterol diet (0.15%) for two months to measure the atherogenic areas of the hearts and aortas. When triacsin C was orally administered (10 mg/kg/day), the atherosclerotic areas were significantly reduced by 86% in aorta and 36% in hearts. The results strongly suggested that triacsin C shows anti-atherogenic activity by inhibiting acyl-CoA synthetase activity.
Matsuda
Daisuke
D
School of Pharmacy, Kitasato University, Shirokane, Tokyo, Japan.
Namatame
Ichiji
I
Ohshiro
Taichi
T
Ishibashi
Shun
S
Omura
Satoshi
S
Tomoda
Hiroshi
H
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D050197:Atherosclerosis / Q000473:pathology / Q000517:prevention & control*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000633:toxicity; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology; D011973:Receptors, LDL / Q000235:genetics; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism; D014226:Triazenes / Q000302:isolation & purification / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002791:Cholesterol, Dietary; D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D011973:Receptors, LDL; D014226:Triazenes; D014280:Triglycerides; C034613:triacsin C; D002784:Cholesterol; D003066:Coenzyme A Ligases