UMMS Affiliation
Program in Molecular Medicine; Department of Medicine, Division of Cardiovascular Medicine; UMass Metabolic Network
Publication Date
2016-08-09
Document Type
Article
Disciplines
Biochemistry | Cardiovascular Diseases | Cell Biology | Cellular and Molecular Physiology | Developmental Biology | Molecular Biology
Abstract
Arterial 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.
Keywords
JNK, MLK, angiogenesis, cell biology, collateral arteries, collaterogenesis, developmental biology, mouse, stem cells
Rights and Permissions
© 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.
DOI of Published Version
10.7554/eLife.18414
Source
Elife. 2016 Aug 9;5. pii: e18414. doi: 10.7554/eLife.18414. Link to article on publisher's site
Journal/Book/Conference Title
eLife
Related Resources
PubMed ID
27504807
Repository Citation
Ramo, Kasmir; Sugamura, Koichi; Craige, Siobhan M.; Keaney, John F. Jr.; and Davis, Roger J., "Suppression of ischemia in arterial occlusive disease by JNK-promoted native collateral artery development" (2016). Davis Lab Publications. 87.
https://escholarship.umassmed.edu/davis/87
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Biochemistry Commons, Cardiovascular Diseases Commons, Cell Biology Commons, Cellular and Molecular Physiology Commons, Developmental Biology Commons, Molecular Biology Commons