Abstract
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.
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