Faculty Collaboration Database

Vascular Actions of Angiotensin 1-7 in the Human Microcirculation: Novel Role for Telomerase. Arterioscler Thromb Vasc Biol 2016 Jun;36(6):1254-62

Date

04/16/2016

Pubmed ID

27079876

Pubmed Central ID

PMC4882242

DOI

10.1161/ATVBAHA.116.307518

Scopus ID

2-s2.0-84963556451 (requires institutional sign-in at Scopus site)   49 Citations

Abstract

OBJECTIVE: This study examined vascular actions of angiotensin 1-7 (ANG 1-7) in human atrial and adipose arterioles.

APPROACH AND RESULTS: The endothelium-derived hyperpolarizing factor of flow-mediated dilation (FMD) switches from antiproliferative nitric oxide (NO) to proatherosclerotic hydrogen peroxide in arterioles from humans with coronary artery disease (CAD). Given the known vasoprotective properties of ANG 1-7, we tested the hypothesis that overnight ANG 1-7 treatment restores the NO component of FMD in arterioles from patients with CAD. Endothelial telomerase activity is essential for preserving the NO component of vasodilation in the human microcirculation; thus, we also tested whether telomerase activity was necessary for ANG 1-7-mediated vasoprotection by treating separate arterioles with ANG 1-7±the telomerase inhibitor 2-[[(2E)-3-(2-naphthalenyl)-1-oxo-2-butenyl1-yl]amino]benzoic acid. ANG 1-7 dilated arterioles from patients without CAD, whereas dilation was significantly reduced in arterioles from patients with CAD. In atrial arterioles from patients with CAD incubated with ANG 1-7 overnight, the NO synthase inhibitor NG-nitro-l-arginine methyl ester abolished FMD, whereas the hydrogen peroxide scavenger polyethylene glycol catalase had no effect. Conversely, in vessels incubated with ANG 1-7+2-[[(2E)-3-(2-naphthalenyl)-1-oxo-2-butenyl1-yl]amino]benzoic acid, NG-nitro-l-arginine methyl ester had no effect on FMD, but polyethylene glycol catalase abolished dilation. In cultured human coronary artery endothelial cells, ANG 1-7 significantly increased telomerase activity. These results indicate that ANG 1-7 dilates human microvessels, and dilation is abrogated in the presence of CAD. Furthermore, ANG 1-7 treatment is sufficient to restore the NO component of FMD in arterioles from patients with CAD in a telomerase-dependent manner.

CONCLUSIONS: ANG 1-7 exerts vasoprotection in the human microvasculature via modulation of telomerase activity.

Author List

Durand MJ, Zinkevich NS, Riedel M, Gutterman DD, Nasci VL, Salato VK, Hijjawi JB, Reuben CF, North PE, Beyer AM

Authors

Andreas M. Beyer PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Matt Durand PhD Associate Professor in the Physical Medicine and Rehabilitation department at Medical College of Wisconsin
Paula E. North MD, PhD Professor in the Pathology department at Medical College of Wisconsin
Natalya S. Zinkevich PhD Research Scientist I in the Medicine department at Medical College of Wisconsin

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

Adipose Tissue
Aged
Angiotensin I
Arterioles
Case-Control Studies
Cells, Cultured
Coronary Artery Disease
Coronary Vessels
Dose-Response Relationship, Drug
Endothelial Cells
Enzyme Inhibitors
Female
Heart Atria
Humans
In Vitro Techniques
Male
Middle Aged
Nitric Oxide
Peptide Fragments
Proto-Oncogene Proteins
Receptors, G-Protein-Coupled
Signal Transduction
Telomerase
Vasodilation
Vasodilator Agents