The shear stress-induced transcription factor klf2 affects dynamics and angiopoietin-2 content of weibel-palade bodies

Ellen L. van Agtmaal, Ruben Bierings, Bieuwke S. Dragt, Thomas A. Leyen, Mar Fernandez-Borja, Anton J.G. Horrevoets, Jan Voorberg*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

35 Citations (Scopus)
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Abstract

Background: The shear-stress induced transcription factor KLF2 has been shown to induce an atheroprotective phenotype in endothelial cells (EC) that are exposed to prolonged laminar shear. In this study we characterized the effect of the shear stress-induced transcription factor KLF2 on regulation and composition of Weibel-Palade bodies (WPBs) using peripheral blood derived ECs. Methodology and Principal Findings: Lentiviral expression of KLF2 resulted in a 4.5 fold increase in the number of WPBs per cell when compared to mock-transduced endothelial cells. Unexpectedly, the average length of WPBs was significantly reduced: in mock-transduced endothelial cells WPBs had an average length of 1.7 μm versus 1.3 μm in KLF2 expressing cells. Expression of KLF2 abolished the perinuclear clustering of WPBs observed following stimulation with cAMP-raising agonists such as epinephrine. Immunocytochemistry revealed that WPBs of KLF2 expressing ECs were positive for IL-6 and IL-8 (after their upregulation with IL-1β) but lacked angiopoietin-2 (Ang2), a regular component of WPBs. Stimulus-induced secretion of Ang2 in KLF2 expressing ECs was greatly reduced and IL-8 secretion was significantly lower. Conclusions and Significance: These data suggest that KLF2 expression leads to a change in size and composition of the regulated secretory compartment of endothelial cells and alters its response to physiological stimuli.

Original languageEnglish
Article numbere38399
JournalPLoS ONE
Volume7
Issue number6
DOIs
Publication statusPublished - 8 Jun 2012
Externally publishedYes

Bibliographical note

Funding:
This work was supported in part by grants from the Netherlands Heart Foundation (Grant 2002.187), the Netherlands Thrombosis Foundation
(TSN2007.01) and the Netherlands Organization for Scientific Research (NWO, grant no. 91209006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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