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. 2009 Mar 15;606(1-3):72-6.
doi: 10.1016/j.ejphar.2008.12.047. Epub 2009 Jan 14.

Pitavastatin suppresses mitogen activated protein kinase-mediated Erg-1 induction in human vascular smooth muscle cells

Brian D Lamon  1 , Barbara D Summers, Antonio M Gotto Jr, David P Hajjar
Affiliations

Pitavastatin suppresses mitogen activated protein kinase-mediated Erg-1 induction in human vascular smooth muscle cells

Brian D Lamon et al. Eur J Pharmacol. .

Abstract

Statins have been demonstrated to elicit a broad range of cellular events resulting in an attenuation of the inflammatory response and enhanced protection to the components of the vessel wall. The present study was designed to examine the effect of pitavastatin on pathways associated with the proinflammatory gene, early growth response (Egr)-1, in human vascular smooth muscle cells. Pretreatment with pitavastatin resulted in a dose-dependent reduction in Egr-1 protein and suppressed Egr-1 mRNA expression in response to phorbol 12-myristate 13-acetate (PMA). A reduction in Egr-1 expression reduced the activation of NGFI-A binding protein (NAB)-2, an Egr-1-dependent gene. Furthermore, these events appeared to be dependent on the ability of pitavastatin to attenuate signaling cascades associated with extracellular regulated kinase (ERK) 1/2, but not p38 and c-Jun N-terminal kinase (JNK).

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Conflict of interest statement

Conflict of Interest Statement: Drs. David P. Hajjar and Antonio M. Gotto Jr. are consultants for Kowa Pharmaceuticals in the area of atherosclerosis research.

Figures

Figure 1
Figure 1
A. Representative western blot and densitometric analysis for time-course activation of Egr-1 in human aortic smooth muscle cells by PMA. B. Representative western blot and densitometric analysis of Egr-1 in cells pretreated with increasing concentrations of pitavastatin (0.01–10μmol/L) prior to 1h stimulation with PMA. C. Western blot of basal Egr-1 expression in response to pitavastatin (1–10μmol/L). D. Quantification of Egr-1 mRNA by real-time PCR. E. Representative western blot of NAB-2 expression in response to pitavastatin (1–20μmol/L) prior to 2h stimulation with PMA. All data normalized to GADPH. *P<0.05 relative to control. † P<0.05 relative to PMA alone.
Figure 2
Figure 2
A. Representative western blot and densitometric analysis of Egr-1 expression in human aortic smooth muscle cells in response to PMA (1h) ± inhibitors of MAPK pathways. B. Representative western blots of phosphorylated MAPKs pretreated with increasing concentrations of pitavastatin (0.01–10μmol/L) prior to 1h stimulation with PMA. C. Densitometric analysis of phosphorylated forms of ERK, p-38 and JNK pretreated with 1μmol/L pitavastatin prior to 1h stimulation with PMA.
See this image and copyright information in PMC

References

    1. Aoki T, Nishimura H, Nakagawa S, Kojima J, Suzuki H, Tamaki T, Wada Y, Yokoo N, Sato F, Kimata H, Kitahara M, Toyoda K, Sakashita M, Saito Y. Pharmacological profile of a novel synthetic inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Arzneimittelforschung. 1997;47:904–909. - PubMed
    1. Bea F, Blessing E, Shelley MI, Shultz JM, Rosenfeld ME. Simvastatin inhibits expression of tissue factor in advanced atherosclerotic lesions of apolipoprotein E deficient mice independently of lipid lowering: potential role of simvastatin-mediated inhibition of Egr-1 expression and activation. Atherosclerosis. 2003;167:187–194. - PubMed
    1. Calabro P, Yeh ET. The pleiotropic effects of statins. Curr Opin Cardiol. 2005;20:541–546. - PubMed
    1. Davignon J. The cardioprotective effects of statins. Curr Atheroscler Rep. 2004;6:27–35. - PubMed
    1. Du B, Fu C, Kent KC, Bush H, Jr, Schulick AH, Kreiger K, Collins T, McCaffrey TA. Elevated Egr-1 in human atherosclerotic cells transcriptionally represses the transforming growth factor-beta type II receptor. J Biol Chem. 2000;275:39039–39047. - PubMed

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