| First Author | Harja E | Year | 2009 |
| Journal | FASEB J | Volume | 23 |
| Issue | 4 | Pages | 1081-91 |
| PubMed ID | 19036858 | Mgi Jnum | J:147225 |
| Mgi Id | MGI:3839712 | Doi | 10.1096/fj.08-120345 |
| Citation | Harja E, et al. (2009) Mice deficient in PKCbeta and apolipoprotein E display decreased atherosclerosis. FASEB J 23(4):1081-91 |
| abstractText | Endothelial activation is a central initiating event in atheroma formation. Evidence from our laboratory and others has demonstrated links between activation of early growth response-1 (Egr-1) and atherosclerosis and also has demonstrated that activated protein kinase C (PKC) betaII is a critical upstream regulator of Egr-1 in response to vascular stress. We tested the role of PKCbeta in regulating key events linked to atherosclerosis and show that the aortas of apoE(-/-) mice display an age-dependent increase in PKCbetaII antigen in membranous fractions vs. C57BL/6 animals with a approximately 2-fold increase at age 6 wk and a approximately 4.5-fold increase at age 24 wk. Consistent with important roles for PKCbeta in atherosclerosis, a significant decrease in atherosclerotic lesion area was evident in PKCbeta(-/-)/apoE(-/-) vs. apoE(-/-) mice by approximately 5-fold, in parallel with significantly reduced vascular transcripts for Egr-1 and matrix metalloproteinase (MMP)-2 antigen and activity vs. apoE(-/-) mice. Significant reduction in atherosclerosis of approximately 2-fold was observed in apoE(-/-) mice fed ruboxistaurin chow (PKCbeta inhibitor) vs. vehicle. In primary murine and human aortic endothelial cells, the PKCbeta-JNK mitogen-activated protein kinase pathway importantly contributes to oxLDL-mediated induction of MMP2 expression. Blockade of PKCbeta may be beneficial in mitigating endothelial perturbation and atherosclerosis. |
