Suppression of ischemia in arterial occlusive disease by JNK-promoted native collateral artery development.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27504807.
- Also identified by DOI 10.7554/eLife.18414 and PMC identifier 4999312.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Arterial Occlusive Diseases
- Femoral Artery
- Ischemia
- MAP Kinase Kinase Kinases
- MAP Kinase Signaling System
- Neovascularization, Physiologic