The EYA3 tyrosine phosphatase activity promotes pulmonary vascular remodeling in pulmonary arterial hypertension

Yuhua Wang, Ram Naresh Pandey, Allen J. York, Jaya Mallela, William C. Nichols, Yueh-Chiang Hu, Jeffery D. Molkentin, Kathryn A. Wikenheiser-Brokamp and Rashmi S. Hegde ()
Additional contact information
Yuhua Wang: University of Cincinnati College of Medicine
Ram Naresh Pandey: University of Cincinnati College of Medicine
Allen J. York: University of Cincinnati College of Medicine
Jaya Mallela: University of Cincinnati College of Medicine
William C. Nichols: University of Cincinnati College of Medicine
Yueh-Chiang Hu: University of Cincinnati College of Medicine
Jeffery D. Molkentin: University of Cincinnati College of Medicine
Kathryn A. Wikenheiser-Brokamp: University of Cincinnati College of Medicine
Rashmi S. Hegde: University of Cincinnati College of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract In pulmonary hypertension vascular remodeling leads to narrowing of distal pulmonary arterioles and increased pulmonary vascular resistance. Vascular remodeling is promoted by the survival and proliferation of pulmonary arterial vascular cells in a DNA-damaging, hostile microenvironment. Here we report that levels of Eyes Absent 3 (EYA3) are elevated in pulmonary arterial smooth muscle cells from patients with pulmonary arterial hypertension and that EYA3 tyrosine phosphatase activity promotes the survival of these cells under DNA-damaging conditions. Transgenic mice harboring an inactivating mutation in the EYA3 tyrosine phosphatase domain are significantly protected from vascular remodeling. Pharmacological inhibition of the EYA3 tyrosine phosphatase activity substantially reverses vascular remodeling in a rat model of angio-obliterative pulmonary hypertension. Together these observations establish EYA3 as a disease-modifying target whose function in the pathophysiology of pulmonary arterial hypertension can be targeted by available inhibitors.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-12226-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12226-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-12226-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().