Journal article
Endothelial-Specific Expression of WNK1 Kinase Is Essential for Angiogenesis and Heart Development in Mice
The American journal of pathology, Vol.175(3), pp.1315-1327
09/2009
DOI: 10.2353/ajpath.2009.090094
PMCID: PMC2731149
PMID: 19644017
Abstract
WNK1 [with-no-lysine (K)−1] is a ubiquitous serine/threonine kinase with a unique placement of the catalytic lysine residue. Increased WNK1 expression levels in humans causes a hypertension-hyperkalemia syndrome by altering renal Na
+
and K
+
transport. The function of WNK1 outside of the kidney remains elusive. In this study, we report that
Wnk1
ablation causes cardiovascular developmental defects. The developing heart of null mutant embryos has smaller chambers and reduced myocardial trabeculation at E10.5. Yolk sac vessels in the E10.5 null mutant fail to remodel into a network of large and small vessels, and embryonic vessels show defective angiogenesis that involves both arteries and veins. The arterial marker neuropilin-1 and venous marker EphB4 are ectopically expressed in mutant veins and arteries, respectively. However, the orphan nuclear receptor COUP-TFII as well as the Notch signaling pathway, which are known to be critical for angiogenesis and artery-vein specification, are not significantly altered in
Wnk1
−/−
mutants. Conditional deletion of
Wnk1
in endothelial cells phenotypically copies defects caused by global
Wnk1
ablation. Moreover, endothelial-specific expression of a
Wnk1
transgene rescues cardiovascular developmental defects in
Wnk1
−/−
mice. These findings identify a novel function of WNK1 in endothelial cells that is critical for angiogenesis and heart development, raising the possibility for a role of endothelial WNK1 in the control of blood pressure and postnatal angiogenesis and cardiac growth.
Details
- Title: Subtitle
- Endothelial-Specific Expression of WNK1 Kinase Is Essential for Angiogenesis and Heart Development in Mice
- Creators
- Jian Xie - From the Departments of MedicineTao Wu - The University of Texas Southwestern Medical CenterKe Xu - From the Departments of MedicineIvan K Huang - From the Departments of MedicineOndine Cleaver - From the Departments of MedicineChou-Long Huang - From the Departments of Medicine
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.175(3), pp.1315-1327
- DOI
- 10.2353/ajpath.2009.090094
- PMID
- 19644017
- PMCID
- PMC2731149
- NLM abbreviation
- Am J Pathol
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Publisher
- American Society for Investigative Pathology
- Language
- English
- Date published
- 09/2009
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984094395302771
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