DIFFERENTIAL EXPRESSION AND ACTIVITY OF P34(CDC2) IN CULTURED AORTIC ADVENTITIAL FIBROBLASTS DERIVED FROM SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS

Objective: The present investigation was undertaken to determine whether p34cdc2, a cell-cycle regulatory kinase, is involved in the manifestation of the altered proliferation evident in fibroblasts isolated from spontaneously hypertensive rats (SHR). Design: Experiments were performed on quiescent aortic adventitial fibroblasts stimulated to re-enter the cell cycle in order to examine the timing of cell cycle-related events. Methods: The cell-cycle phase was determined by flow cytometry and was related to the cellular content and kinase activity of p34cdc2. Results: SHR fibroblasts displayed a heightened basal level of p34cdc2 at quiescence relative to Wistar-Kyoto (WKY) rat cells. Both SHR and WKY fibroblasts showed a cell cycle-dependent increase in p34cdc2 content, beginning in S phase. However, the SHR adventitial fibroblasts exited G0-G1 several hours earlier than the WKY fibroblasts as indicated by the time of initiation of DNA synthesis and increase in activity of p34cdc2. Conclusions: SHR aortic adventitial fibroblasts appear to have a heightened proliferative capacity relative to WKY fibroblasts, which is evident in a quicker exit from G0 and faster transition to DNA synthesis, followed. by the earlier activation of p34cdc2.