Suppression of ischemia in arterial occlusive disease by JNK-promoted native collateral artery development
UMass Chan AffiliationsUMass Metabolic Network
Department of Medicine, Division of Cardiovascular Medicine
Program in Molecular Medicine
Document TypeJournal Article
Cellular and Molecular Physiology
MetadataShow full item record
AbstractArterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. We report that disruption of the mixed-lineage protein kinase (MLK) - cJun NH2-terminal kinase (JNK) signaling pathway in endothelial cells causes severe blockade of blood flow and failure to recover in the murine femoral artery ligation model of hindlimb ischemia. We show that the MLK-JNK pathway is required for the formation of native collateral arteries that can restore circulation following arterial occlusion. Disruption of the MLK-JNK pathway causes decreased Dll4/Notch signaling, excessive sprouting angiogenesis, and defects in developmental vascular morphogenesis. Our analysis demonstrates that the MLK-JNK signaling pathway is a key regulatory mechanism that protects against ischemia in arterial occlusive disease.
SourceElife. 2016 Aug 9;5. pii: e18414. doi: 10.7554/eLife.18414. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/28362
Related ResourcesLink to Article in PubMed
Rights© 2016, Ramo et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Except where otherwise noted, this item's license is described as © 2016, Ramo et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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