Ghrelin inhibits foam cell formation via simultaneously down-regulating the expression of acyl-coenzyme A:cholesterol acyltransferase 1 and up-regulating adenosine triphosphate-binding cassette transporter A1.
BACKGROUND
Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), revealed cardioprotective effects in both experimental models and human. There is far less information on the mechanisms that produce antiatherogenic effects. We assessed the expression of acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT-1) and adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1), which have been implicated in regulating cellular cholesterol homeostasis and therefore play critical roles in foam cell formation, in THP-1-derived foam cells in the presence of various concentration of ghrelin.


METHODS
After 48 h of culture in the presence of phorbol myristate acetate, THP-1 monocytes differentiated to macrophages. After another 24 h of culture with ox-LDL, the differentiated cells transformed to foam cells. Different concentrations of ghrelin and other intervention factors were added, respectively. The expression of ACAT-1 and ABCA1 was detected by a technique in molecular biology. The content of cellular cholesterol was measured by zymochemistry via a fluorospectrophotometer.


RESULTS
Ghrelin could down-regulate the expression of ACAT-1 and up-regulate the expression of ABCA1 in a dose-dependent manner simultaneously. Ghrelin also decreased cellular cholesterol content and increased cholesterol efflux. These effects could be abolished by the specific antagonist of GHS-R and a peroxisome proliferator-activated receptor γ (PPARγ)-specific inhibitor, respectively.


CONCLUSIONS
The results suggest that ghrelin inhibited foam cell formation via simultaneously down-regulating the expression of ACAT-1 and up-regulating ABCA1. Those effects may be achieved via pathways involving GHS-R and PPARγ.
Cheng
Bei
B
Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. chengbei81@yahoo.cn
Wan
Jingjing
J
Wang
Yanfu
Y
Mei
Chunli
C
Liu
Wei
W
Ke
Li
L
He
Ping
P
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000101:Acetyl-CoA C-Acetyltransferase / Q000096:biosynthesis*; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D015536:Down-Regulation; D005487:Foam Cells / Q000166:cytology / Q000378:metabolism*; D054439:Ghrelin / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000166:cytology; D047495:PPAR gamma / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D054439:Ghrelin; D047495:PPAR gamma; D054440:Receptors, Ghrelin; D002784:Cholesterol; C506639:ACAT1 protein, human; D000101:Acetyl-CoA C-Acetyltransferase