The objective of this proposal is to reveal how the local hemodynamic environment alters the function of protein kinase C in aortic endothelial cells. To study the steady-state in vivo, we will utilize protein from freshly isolated endothelial cells in regions of disturbed flow (inner aortic arch) and undisturbed flow (descending thoracic aorta) of normal adult pigs.
The first aim will seek to identify the responsible isozymes and understand the mechanism behind our observation that PKC activity is increased in DF regions.
The second aim will use proteomics to identify those proteins which interact with or are substrates for PKC. This information is critical for our attempts to understand the consequences of an focal increase in PKC activity. Thus, this project will provide novel information on the steady-state differences between athero-prone and athero-protected endothelial cells. This in turn has the potential to suggest novel pathways for anti-atherosclerotic interventions. ? ?
| Magid, Richard; Davies, Peter F (2005) Endothelial protein kinase C isoform identity and differential activity of PKCzeta in an athero-susceptible region of porcine aorta. Circ Res 97:443-9 |
