Item type:Thesis, Open Access

Die Rolle der Ca2+ -aktivierten K+ -Kanäle bei Endothelzellproliferation und Angiogenese

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Date

2006-08-16

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Philipps-Universität Marburg
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Abstract

OBJECTIVE: Ca2+-activated K+ (K(Ca)) channels have been proposed to promote mitogenesis in several cell types. Here, we tested whether the intermediate-conductance K(Ca) channel (IKCa1) and the large-conductance K(Ca) channel (BK(Ca)) contribute to endothelial cell (EC) proliferation and angiogenesis. MATERIAL AND RESULTS: Function and expression of IKCa1 and BK(Ca)/Slo were investigated by patch-clamp analysis and real-time RT-PCR in human umbilical vein ECs (HUVECs) and in dermal human microvascular ECs 1 (HMEC-1). HMEC-1 expressed IKCa1 and BK(Ca)/Slo, whereas HUVECs expressed IKCa1. A 48-hour exposure to basic fibroblast growth factor (bFGF) augmented IKCa1 current amplitudes and induced a 3-fold increase in IKCa1 mRNA expression in HUVECs and HMEC-1. Vascular endothelial growth factor (VEGF) was also effective in upregulating IKCa1. BK(Ca)/Slo expression and current amplitudes in HMEC-1 were not altered by bFGF. bFGF- and VEGF-induced EC proliferation was suppressed by charybdotoxin, clotrimazole, or the selective IKCa1 blocker 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), whereas inhibition of BK(Ca)/Slo by iberiotoxin was ineffective. In the Matrigel plug assay in mice, administration of TRAM-34 for 2 weeks significantly suppressed angiogenesis by approximately 85%. CONCLUSIONS: bFGF and VEGF upregulate expression of IKCa1 in human ECs. This upregulation of IKCa1 seems to be required for mitogen-induced EC proliferation and angiogenesis in vivo. Selective IKCa1 blocker might be of therapeutic value to prevent tumor angiogenesis.

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Dates
Created: 2005Issued: 2006-08-16Updated: 2011-08-10
DOI
https://doi.org/10.17192/z2006.0475
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
IKCa1-KanalKanalblockerAngiogenesisTumorangiogeneseEndothelial cell proliferationCa2+ -aktivierte K+ -KanälePotassium channel
DFG-subjects
Patch-Clamp-MethodeIonenkanalTumorwachstumProliferationAngiogeneseEndothelzellePolymerase-KettenreaktionKaliumkanalGenexpressi
DDC-Numbers
610
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2006.0475
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Grgic, Ivica: Die Rolle der Ca2+ -aktivierten K+ -Kanäle bei Endothelzellproliferation und Angiogenese. : Philipps-Universität Marburg 2006-08-16. DOI: https://doi.org/10.17192/z2006.0475.

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This item has been published with the following license: In Copyright