Referenced in: none

Automatically associated channels: TRP , TRPM , TRPM4

Title: TRPM4 inhibition promotes angiogenesis after ischemic stroke.

Authors: Kok Poh Loh, Gandi Ng, Chye Yun Yu, Chee Kong Fhu, Dejie Yu, Rudi Vennekens, Bernd Nilius, Tuck Wah Soong, Ping Liao

Journal, date & volume: Pflugers Arch., 2014 Mar , 466, 563-76

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24043570

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.