Key result
SHR aortic adventitial fibroblasts demonstrated a quicker exit from G0 and faster transition to DNA synthesis, followed by earlier activation of p34cdc2 compared to WKY fibroblasts.
Aortic adventitial fibroblasts from spontaneously hypertensive rats exhibit heightened proliferative capacity and earlier activation of the cell-cycle regulatory kinase p34cdc2 compared to normotensive controls.
May implicate fibroblast cell-cycle dysregulation in hypertensive vascular remodeling; leaves open translational relevance to humans.
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.
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Venance et al. (1993) studied Hypertension. Spontaneously hypertensive rat (SHR) derived fibroblasts vs. Wistar-Kyoto (WKY) rat derived fibroblasts was evaluated on Cell-cycle phase, cellular content, and kinase activity of p34cdc2. SHR aortic adventitial fibroblasts demonstrated a quicker exit from G0 and faster transition to DNA synthesis, followed by earlier activation of p34cdc2 compared to WKY fibroblasts.
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