Activation of PKC beta(II) and PKC theta is essential for LDL-induced cell proliferation of human aortic smooth muscle cells via Gi-mediated Erk1/2 activation and Egr-1 upregulation

Abstract

Native LDL may be a mitogenic stimulus of VSMC proliferation in lesions where endothelial disruption occurs. Recent studies have demonstrated that the mitogenic effects of LDL are accompanied by Erk1/2 activation via an unknown G-protein-coupled receptor (GPCR). In this article, we report that LDL translocated PKC beta(II) and PKC theta from cytosol to plasma membrane, and inhibition of PKC beta(II) and PKC theta decreased LDL effects via the deactivation of Erk1/2. Moreover, pertussis toxin, but not cholera toxin or heparin, inhibited LDL-induced translocation of PKC beta(II) and PKC theta, suggesting that Gi protein plays a role in LDL effects. Of LPA, SIP, and LDL, whose signaling is conveyed via Gi/o proteins, only LDL induced translocation of PKC beta(II) and PKC theta. Inhibition of PKC beta(II) or PKC theta, as well as of Erk1/2 and GPCR, decreases LDL-induced upregulation of Egr-1, which is critical for cell proliferation. This is the first report, to our knowledge, that the participation of PKC theta in VSMC proliferation is unique. (C) 2008 Elsevier Inc. All rights reserved.