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MEF2 activity is required for maintenance of endothelial barrier function and vessel integrity
Author(s) -
Schwarz John J,
Adam Alejandro P,
Herron Crystal R,
Vincent Peter A
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.235.7
Subject(s) - ve cadherin , microbiology and biotechnology , endothelium , barrier function , tight junction , biology , endothelial stem cell , chemistry , biochemistry , in vitro , genetics
Transcription factors of the MEF2 family are critical regulators of the development and physiology of several organ systems. We are investigating their role in the endothelium by the combined endothelial‐specific deletion of Mef2c and global deletion of Mef2a. This results in hemorrhage and death during embryonic development, indicating that the MEF2s are required for vessel integrity. We explored the possibility that the MEF2s are critical for endothelial barrier function by blocking MEF2 activity in a mature monolayer of human dermal microvascular endothelial cells (HDMEC) with an adenovirus expressing a dominant negative MEF2 (DN‐MEF2). Expression of DN‐MEF2 decreased the barrier function of EC monolayers as assessed by changes in transendothelial resistance (TEER) beginning 30 hrs post infection and produced gaps in the endothelial junctions as assessed by immunofluorescence to ZO‐1 and VE‐cadherin. We also found that the thrombin‐induced increase in permeability was enhanced by DN‐MEF2 prior to the onset of increased basal permeability. These results demonstrate that the MEF2s play a role in the regulation of endothelial monolayer integrity. RO1‐HL77870