Study of ATP-binding cassette transporter A1 (ABCA1)-mediated cellular cholesterol efflux in diabetic golden hamsters.
The effects of cyclic adenosine monophosphate (cAMP) and atorvastatin on macrophage adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux were investigated in a diabetic animal model. Golden hamsters were fed a high-fat diet which resulted in insulin resistance. Diabetes was induced by a single intraperitoneal injection of streptozotocin (30 mg/kg). Normal golden hamsters were used as controls. Peritoneal macrophages were incubated with apolipoprotein A-1 (apoA-1), 8-bromoadenosine-3',5'-cyclic monophosphate (8-br-cAMP), and atorvastatin in vitro. Intracellular cholesterol accumulation was greater in the diabetic animals than in the insulin-resistant animals. Expression of ABCA1 mRNA in macrophages from diabetic animals was upregulated by 8-br-cAMP and atorvastatin. ApoA-1 caused a time-dependent cellular cholesterol efflux. Both atorvastatin and 8-br-cAMP significantly facilitated ABCA1-mediated cellular cholesterol efflux, with the maximal cholesterol efflux rate observed in the macrophages from diabetic animals. Accumulation of cholesterol in the macrophages of diabetic animals can be significantly alleviated by atorvastatin or 8-br-cAMP through improving ABCA1-mediated cellular cholesterol efflux.
Zhu
Y
Y
Division of Cardiology, Department of Internal Medicine, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Wang
H-J
HJ
Chen
L-F
LF
Fang
Q
Q
Yan
X-W
XW
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000494:pharmacology; D000069059:Atorvastatin; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004041:Dietary Fats; D004338:Drug Combinations; D015870:Gene Expression / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D004041:Dietary Fats; D004338:Drug Combinations; D006538:Heptanoic Acids; D011758:Pyrroles; D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002784:Cholesterol; D000069059:Atorvastatin