Pitavastatin suppresses mitogen activated protein kinase-mediated Erg-1 induction in human vascular smooth muscle cells.
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).
Lamon
Brian D
BD
Department of Pathology and Laboratory Medicine, Center of Vascular Biology, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA. bdl2001@med.cornell.edu
Summers
Barbara D
BD
Gotto
Antonio M
AM
Hajjar
David P
DP
D000818:Animals; D051766:Early Growth Response Protein 1 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects*
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D011804:Quinolines; D020928:Mitogen-Activated Protein Kinases; C108475:pitavastatin