HMG-CoA reductase inhibitor, simvastatin improves reverse cholesterol transport in type 2 diabetic patients with hyperlipidemia.
OBJECTIVE
ApoA-I and HDL promote cellular cholesterol efflux in the early stages of the reverse cholesterol transport (RCT) pathway. A low plasma HDL-C level is characteristic of atherogenic dyslipidemia in patients with type 2 diabetes. We evaluated plasma lipid levels and the expression of factors related to RCT in type 2 diabetic patients, and the effects of an HMG-CoA reductase inhibitor, simvastatin, were studied.


METHODS
Messenger RNA (mRNA) expression in circulating mononuclear cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), focusing on the following factors: liver X receptor alpha (LXR alpha), ATP-binding cassette A1 (ABCA1), scavenger receptor class B type 1 (SR-B1), apolipoprotein E (ApoE), apolipoprotein A-1 (ApoA-1), caveolin, and cholesterol ester transfer protein (CETP). Type 2 diabetic subjects (n=29) were divided into three subgroups: patients with normolipidemia (DM group, n=11), patients with untreated hyperlipidemia (DMHL group, n=10), and those with hyperlipidemia treated with simvastatin 5-10mg/day (DMST group, n=8). The control group (CNT group) included seven healthy volunteers.


RESULTS
Simvastatin treatment significantly increased plasma levels of ApoA-I compared to the other three groups. Simvastatin treatment improved the expression of mRNA for LXRalpha, ABCA1, and ApoA-I compared with DMHL or control groups.


CONCLUSIONS
Our data suggest that RCT may be reduced in type 2 diabetic patients with hyperlipidemia, and simvastatin may be able to improve reverse cholesterol transport for this population of diabetic patients.
Guan
Jing-Zhi
JZ
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine.
Tamasawa
Naoki
N
Murakami
Hiroshi
H
Matsui
Jun
J
Tanabe
Jutaro
J
Matsuki
Kota
K
Yamashita
Maki
M
Suda
Toshihiro
T
D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D015870:Gene Expression; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006949:Hyperlipidemias / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000494:pharmacology*
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D019821:Simvastatin