Troglitazone and rosiglitazone inhibit the low density lipoprotein-induced vascular smooth muscle cell growth

Summary:

Troglitazone (TRO) and rosiglitazone (RSG) belong to the thiazolidinedione class (insulin-sensitizing agents) and exert many of their metabolic effects as peroxisome proliferator-activated receptor γ (PPAR γ) ligands. In the present study we examined the effects of TRO and RSG on LDL-induced VSMC growth. Pretreatment of VSMC with 1 μM TRO or 0.1 μM RSG completely blocked the LDL-induced cell proliferation as measured by [³H]thymidine incorporation into DNA and by determination of the cell number. We then examined with Western blotting whether these growth suppressing effects are mediated through the mitogen-activated protein kinase (MAPK) pathway, a common signaling pathway activated by growth factors. TRO and RSG had no effect on the LDL-induced stimulation of the MAP kinases ERK1/2, p38 and SAP/JNK. We conclude that thiazolidinediones are potent inhibitors of LDL-induced VSMC growth acting downstream of the cytoplasmic activation of MAPK.

Abbreviations: bFGF basic fibroblast growth factor; DMSO dimethyl sulfoxide; EGF epidermal growth factor; ERK1/2 extracellular signal-response kinases (also termed p44^mapk/p42^mapk); SAPK/JNK stress-activated protein kinase/c-Jun N-terminal kinases; LDL low density lipoprotein; MAPK mitogen-activated protein kinase; MEK ERK kinase; PDVF polyvinylidene difluoride; PPARγ peroxisome proliferator-activated receptor γ; RSG rosiglitazone; TRO troglitazone; VSMC vascular smooth muscle cell(s); RXR retinoid X receptor.

Key words:

Troglitazone - rosiglitazone - oral antidiabetic drugs - low density lipoprotein - MAP kinase

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