Faculty Collaboration Database

Interaction between Mas1 and AT1RA contributes to enhancement of skeletal muscle angiogenesis by angiotensin-(1-7) in Dahl salt-sensitive rats. PLoS One 2020;15(4):e0232067

Date

04/24/2020

Pubmed ID

32324784

Pubmed Central ID

PMC7179868

DOI

10.1371/journal.pone.0232067

Scopus ID

2-s2.0-85083695035 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

The heptapeptide angiotensin-(1-7) (Ang-(1-7)) is protective in the cardiovascular system through its induction of vasodilator production and angiogenesis. Despite acting antagonistically to the effects of elevated, pathophysiological levels of angiotensin II (AngII), recent evidence has identified convergent and beneficial effects of low levels of both Ang-(1-7) and AngII. Previous work identified the AngII receptor type I (AT1R) as a component of the protein complex formed when Ang-(1-7) binds its receptor, Mas1. Importantly, pharmacological blockade of AT1R did not alter the effects of Ang-(1-7). Here, we use a novel mutation of AT1RA in the Dahl salt-sensitive (SS) rat to test the hypothesis that interaction between Mas1 and AT1R contributes to proangiogenic Ang-(1-7) signaling. In a model of hind limb angiogenesis induced by electrical stimulation, we find that the restoration of skeletal muscle angiogenesis in SS rats by Ang-(1-7) infusion is impaired in AT1RA knockout rats. Enhancement of endothelial cell (EC) tube formation capacity by Ang-(1-7) is similarly blunted in AT1RA mutant ECs. Transcriptional changes elicited by Ang-(1-7) in SS rat ECs are altered in AT1RA mutant ECs, and tandem mass spectrometry-based proteomics demonstrate that the protein complex formed upon binding of Ang-(1-7) to Mas1 is altered in AT1RA mutant ECs. Together, these data support the hypothesis that interaction between AT1R and Mas1 contributes to proangiogenic Ang-(1-7) signaling.

Author List

Exner EC, Geurts AM, Hoffmann BR, Casati M, Stodola T, Dsouza NR, Zimmermann M, Lombard JH, Greene AS

Author

Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin I
Animals
Electric Stimulation
Male
Mass Spectrometry
Models, Animal
Muscle, Skeletal
Mutation
Neovascularization, Physiologic
Peptide Fragments
Proteomics
Proto-Oncogene Proteins
Rats
Rats, Inbred Dahl
Receptor, Angiotensin, Type 1
Receptors, G-Protein-Coupled
Signal Transduction