Signaling responses to vascular cell injury

Abstract

Background. Cardiovascular disease is a major cause of death and disability and treatment options are limited. Abnormal vascular smooth muscle cell (VSMC) proliferation is a key pathological feature in atherosclerosis, hypertension, and stenosis and restenosis. In order to design new and effective strategies to cure or prevent cardiovascular disease, it is important to better understand mechanisms of gene transcription, mRNA translation and related signaling pathways. Objective. The aims of this thesis were (i) to understand the function of YrdC in translational control in VSMC, and (ii) to dissect the signal transduction pathways underlying IL-1β-induced Egr-1 expression via MEK in VSMC. Results. In the first study, YrdC, which is upregulated after VSMC injury, was found to play a role in translational regulation, i.e. YrdC positively regulates protein synthesis. In the second study, the involvement of EGFR (tyrosine 845 phosphorylation) in IL-1β-induced Egr-1 expression was demonstrated in both VSMCs and mouse embryonic fibroblasts (MEF) and to mediate IL-1β-induced VSMC migration and proliferation. Conclusion. YrdC, once induced, may play a key role in promoting cell migration or proliferation by mediating protein synthesis in the reparative response to injury in VSMCs. IL-1β-induced Egr-1 expression is mediated through EGFR in VSMCs. These findings provide important insights on signaling responses to vascular cell injury.