Background: The formation and accumulation of foam cells in the vessel wall is one of the hallmarks of the developing atherosclerosis. Generally, it is accepted that foam cells are transdifferentiated primarily from the monocytes recruited to the site of developing atheroma. Although there has been studies showed evidence that the presence of VSMC derived foam cells, the understanding of mechanism of lipid uptake in SMCs is still very limited. One of the candidate factors expected to play an important role is PPARΓ1, and the purpose of the present study was to determine whether PPARΓ1 overexpression contributes to cellular lipid accumulation and subsequent foam cell like morphologic change in rVSMCs.
Methods: We employed adenoviral gene delivery system to overexpress PPARΓ1 in rVSMCs. Cells were infected with either Ad/PPARΓ1 or Ad/dnPPARΓ1 lacking ligand binding domain, or Ad/LacZ as control. Each group was incubated with or without 5 μM of troglitazone, a synthetic ligand for PPARΓ1, for 3 to 7 days before various analyses. Lipid laden foam cell like morphological change was investigated by Oil red O staining and flow cytometry analysis also investigated lipid content. The expression of related proteins gene were analyzed by Western blot and RT-PCR analysis.
Results: We found that lipid accumulation and morphological changes of VSMC evident between 3 and 7 days after PPARΓ1 overexpression with troglitazone. Dramatic mRNA induction for adipocyte differentiation genes including aP2, adiponectin and CD36 in troglitazone treated Ad/PPARΓ1 overexpressing cells but not after Ad/LacZ or Ad/dnPPARΓ1. The induction of PPARΓ1 expression and its subsequent activation precede the scavenger receptor CD36 activation in the process of atherosclerosis and might be one of the crucial events in VSMC derived foam cell formation.
Conclusions: This study demonstrated that Ad/PPARΓ1 activation stimulates changes of rVSMC phenotypes to adipogenic transformation and lipid accumulation with adipogenesis and lipid metabolism related gene expression.
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