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

Link to Article in PubMed

PubMed ID

27504807

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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