Title: TRPM4 inhibition promotes angiogenesis after ischemic stroke
Authors: Loh, Kok Poh ×
Ng, Gandi
Yu, Chye Yun
Fhu, Chee Kong
Yu, Dejie
Vennekens, Rudi
Nilius, Bernd
Soong, Tuck Wah
Liao, Ping #
Issue Date: Mar-2014
Publisher: Springer-Verlag
Series Title: Pflügers Archiv: European Journal of Physiology vol:466 issue:3 pages:563-76
Abstract: Transient receptor potential melastatin 4 (TRPM4) is a voltage-dependent, nonselective cation channel. Under pathological conditions, sustained activation of TRPM4 leads to oncotic cell death. Here, we report the upregulation of TRPM4 in vascular endothelium following hypoxia/ischemia in vitro and in vivo. In human umbilical vein endothelial cells, TRPM4 expression was increased at both the mRNA and protein levels following oxygen-glucose deprivation. Blocking TRPM4 with 9-phenanthrol greatly enhanced tube formation on Matrigel. In a rat permanent middle cerebral artery occlusion model, TRPM4 was upregulated in the vascular endothelium within the penumbra region after stroke. TRPM4 expression peaked 1 day post-occlusion and gradually decreased. In vivo siRNA-mediated TRPM4 silencing enhanced angiogenesis and improved capillary integrity. A twofold reduction in infarct volume and a substantial recovery of motor function were observed in animals receiving the siRNA treatment. Interestingly, the protective effect of TRPM4 suppression disappeared 5 days after stroke induction, indicating that TRPM4 upregulation is critical for cerebral damage during the acute phase of stroke. TRPM4 could be a potential therapeutic target for ischemic stroke.
ISSN: 0031-6768
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Cellular and Molecular Medicine - miscellaneous
× corresponding author
# (joint) last author

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