scholarly journals The GPER1 Agonist G-1 Attenuates Endothelial Cell Proliferation by Inhibiting DNA Synthesis and Accumulating Cells in the S and G2 Phases of the Cell Cycle

2011 ◽  
Vol 48 (4) ◽  
pp. 327-335 ◽  
Author(s):  
Anders Holm ◽  
Bo Baldetorp ◽  
Björn Olde ◽  
L.M. Fredrik Leeb-Lundberg ◽  
Bengt-Olof Nilsson
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endothelial Cell ◽  
Dna Synthesis ◽  
Endothelial Cell Proliferation

scholarly journals Inhibition of endothelial cell proliferation by platelet factor-4 involves a unique action on S phase progression.

1994 ◽  
Vol 127 (4) ◽  
pp. 1121-1127 ◽  
Author(s):  
S K Gupta ◽  
J P Singh
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Dna Synthesis ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Endothelial Cell Proliferation ◽  
Platelet Factor ◽  
Cycle Progression

Modulation of endothelial cell proliferation and cell cycle progression by the "chemokine" platelet factor-4 (PF-4) was investigated. PF-4 inhibited DNA synthesis, as well as proliferation of endothelial cells derived from large and small blood vessels. Inhibition by PF-4 was independent of the type and the concentration of stimuli used for the induction of endothelial cell proliferation. Inhibition of cell growth by PF-4 was reversible. The effects of PF-4 were antagonized by heparin. Cell cycle analysis using [3H]thymidine pulse labeling during traverse of synchronous cells from G0/G1 to S phase revealed that addition of PF-4 during G1 phase completely abolished the entry of cells into S phase. In addition, PF-4 also inhibited DNA synthesis in cells that were already in S phase. In exponentially growing cells, addition of PF-4 resulted in an accumulation of > 70% of the cells in early S phase, as determined by FACS (Becton-Dickinson Immunocytometry Systems, Mountain View, CA). In cells synchronized in S phase by hydroxyurea and then released, addition of PF-4 promptly blocked further progression of DNA synthesis. These results demonstrate that in G0/G1-arrested cells, PF-4 inhibited entry of endothelial cells into S phase. More strikingly, our studies have revealed a unique mode of endothelial cell growth inhibition whereby PF-4 effectively blocked cell cycle progression during S phase.

Inhibition of Human Umbilical Vein Endothelial Cell Proliferation by the CXC Chemokine, Platelet Factor 4 (PF4), Is Associated With Impaired Downregulation of p21Cip1/WAF1

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Grazia Gentilini ◽  
Nancy E. Kirschbaum ◽  
James A. Augustine ◽  
Richard H. Aster ◽  
Gian Paolo Visentin
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endothelial Cell ◽  
Umbilical Vein ◽  
Cyclin E ◽  
Endothelial Cell Proliferation ◽  
Cyclin Dependent Kinase ◽  
Platelet Factor ◽  
Human Umbilical Vein ◽  
Cdk2 Activity

Human PF4 is a heparin-binding chemokine known to be capable of inhibiting endothelial cell proliferation and angiogenesis. To explore the biological mechanisms responsible for this action, we investigated the effect of PF4 on epidermal growth factor (EGF)-stimulated human umbilical vein endothelial cells (HUVEC), a model system in which stimulation is essentially independent of interaction with cell-surface glycosaminoglycans. Based on previous findings that PF4 blocks endothelial cell cycle entry and progression into S phase, we studied the molecular mechanism(s) of PF4 interference with cell cycle machinery. PF4 treatment of EGF-stimulated HUVEC caused a decrease in cyclin E–cyclin-dependent kinase 2 (cdk2) activity with resulting attenuation of retinoblastoma protein phosphorylation. PF4-dependent downregulation of cyclin E-cdk2 activity was associated with increased binding of the cyclin-dependent kinase inhibitor, p21Cip1/WAF1, to the cyclin E-cdk2 complex. Analysis of total cellular p21Cip1/WAF1 showed that in the presence of PF4, p21Cip1/WAF1 levels were sustained at time points when p21Cip1/WAF1 was no longer detectable in cells stimulated by EGF in the absence of PF4. These findings indicate that PF4 inhibition of HUVEC proliferation in response to EGF is associated with impaired downregulation of p21Cip1/WAF1 and provide the first evidence for interference with cell cycle mechanisms by a chemokine.

Selective inhibition of cyclooxygenase (COX)-2 inhibits endothelial cell proliferation by induction of cell cycle arrest

2004 ◽  
Vol 113 (4) ◽  
pp. 541-548 ◽  
Author(s):  
Kentaro Yazawa ◽  
Nelson H. Tsuno ◽  
Joji Kitayama ◽  
Kazushige Kawai ◽  
Yurai Okaji ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endothelial Cell ◽  
Cell Cycle Arrest ◽  
Selective Inhibition ◽  
Endothelial Cell Proliferation ◽  
Cycle Arrest ◽  
Cox 2

scholarly journals Cell Cycle-dependent Phosphorylation of the RUNX2 Transcription Factor by cdc2 Regulates Endothelial Cell Proliferation

2006 ◽  
Vol 281 (11) ◽  
pp. 7118-7128 ◽  
Author(s):  
Meng Qiao ◽  
Paul Shapiro ◽  
Matthew Fosbrink ◽  
Horea Rus ◽  
Rakesh Kumar ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Endothelial Cell ◽  
Endothelial Cell Proliferation ◽  
Cycle Dependent
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