Objective      To identified the role of peroxisome proliferator-activated receptor δ (PPARδ) and its possible mechanisms during the formation of vascular smooth muscle cells (VSMCs)-derived foam cells.       Methods      Primary VSMCs were isolated from male C57BL/6J mice by tissue attached methods. VSMCs were induced by oxidized low density lipoprotein (ox-LDL) to form foam cells. The protein expression of PPARδ was detected by Western blotting in 24

48 and 72 h after ox-LDL treatment. Furthermore

PPARδ agonist

GW0742 (25 nmol/L)

and its inhibitor

GSK0660 (1 μmol/L) were used to regulate PPARδ for the role of the molecule in the formation. VSMCs were treated respectively by ox-LDL (50 μg/mL)

GW0742+ox-LDL (50 μg/mL)

and GSK0660+ox-LDL (50 μg/mL)

and the cells without treatment served as control. In 48 h after above treatment

Oil Red O staining was used to observe intracellular lipid deposition. Protein levels of PPARδ and acyl coenzyme A-cholesterol acyltransferase 1 (ACAT1) were determined by Western blotting

and then the levels were analyzed to explore the role of PPARδ during the formation of foam cells and its relationship with ACAT1.       Results      The protein level of PPARδs was reduced in a time-dependent manner during the formation of foam cells derived from VSMCs

reached the lowest at the 48th hour by 29% reduction (vs control

P0.05)

and then maintained at a low level. The addition of GW0742 obviously reduced the intracellular cholesterol content by about 55% (vs ox-LDL group， P0.05) in VSMCs

while GSK0660 significantly increased intracellular cholesterol content by about 20% (vs ox-LDL group

P0.05). In addition

GW0742 treatment decreased the protein level of ACAT1 by about 28% 0% (vs ox-LDL group

P0.05). However

GSK0660 elevated the level of ACAT1 by about 29% (vs ox-LDL group

P0.05).       Conclusion      Activation of PPARδ suppresses the formation of foam cells from VSMCs by down-regulating the expression of ACAT1.