© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
T-cadherin upregulation correlates with cell-cycle progression and promotes proliferation of vascular cells
aDepartment of Research, Cardiovascular Laboratories, Basel University Hospital, ZLF 316, Hebelstrasse 20, CH 4031 Basel, Switzerland
bDivision of Cardiology, Kantonsspital Luzern, CH 6000 Luzern, Switzerland
* Corresponding author. Tel.: +41-61-265-2422; fax: +41-61-265-2350. E-mail address: Therese-J.Resink{at}unibas.ch
Objective: In vascular tissue, T-cadherin (T-cad) levels correlate with the progression of atherosclerosis, restenosis and tumour neovascularization. This study investigates whether T-cad influences proliferation of vascular cells. Methods and Results: Cultures of human umbilical vein endothelial cells (HUVEC) and rat and human aortic smooth muscle cells (rSMC, hSMC) were used. T-cad was overexpressed in HUVEC and hSMC using an adenoviral expression system. In cultures released from G1/G0 synchrony parallel immunoblot analysis of T-cad and cell cycle phase specific markers (p27Kip1, cyclin D1, E2F1, PCNA, cyclin B) showed increased T-cad protein levels subsequent to entry into early S-phase with sustained elevation through S-and M-phases. T-cad was increased in G2/M-phase (colchicine) synchronized cultures. In FACS-sorted cell populations, expression of T-cad in S-and G2/M-phase was higher than G1/G0-phase. Compared with empty-and LacZ-vector infected controls, HUVEC and hSMC overexpressing T-cad exhibited increased proliferation as assessed in enumeration and DNA synthesis assays. Additionally, following release from G1/G0 synchrony, HUVEC and hSMC overexpressing T-cad enter S-phase more rapidly. Flow cytometry after BrdU/propidium labelling confirmed increased cell cycle progression in T-cad overexpressing cells. Conclusion: In vascular cells, T-cad is dynamically regulated during the cell cycle and its expression functions in the promotion of proliferation. T-cad may facilitate progression of proliferative vascular disorders such as atherosclerosis, restenosis and tumour angiogenesis.
KEYWORDS T-cadherin; Vascular cells; Cell cycle; Proliferation; Adenoviral expression
Time for primary review 36 days
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