Exp Clin Endocrinol Diabetes 2001; Vol. 109(4): 203-209
DOI: 10.1055/s-2001-15107
Articles

© Johann Ambrosius Barth

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

I. Gouni-Berthold 1 , H. K. Berthold 2 , A.-A. Weber 3 , C. Seul 1 , H. Vetter 1 , A. Sachinidis 1, 4
  • 1 Medizinische Universitäts-Poliklinik, Bonn, Germany
  • 2 Institut für Klinische Forschung/Abteilung Klinische Pharmakologie, Herz- und Kreislaufzentrum, Rotenburg an der Fulda, Germany
  • 3 Institut für Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany
  • 4 Present address: Institut für Neurophysiologie, Universität zu Köln, Köln, Germany
Further Information

Publication History

Publication Date:
31 December 2001 (online)

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 p44mapk/p42mapk); 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.

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Professor Dr. A. Sachinidis

Institut für Neurophysiologie

Universität zu Köln

Robert-Koch-Str. 39

50931 Köln

Germany

Phone: +49-221-4787373

Fax: +49-221-4786965

Email: A.Sachinidis@uni-koeln.de

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