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

Abstract

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.