Angiotensin-(1-7) Reverses Angiogenic Dysfunction in Corpus Cavernosum by Acting on the Microvasculature and Bone Marrow-derived Cells in Diabetes

Overview

Journal J Sex Med

Publisher Oxford University Press

Specialties Gynecology & Obstetrics
Reproductive Medicine
Urology

Date 2014 Jun 24

PMID 24953642

Citations 9

Authors

Neha Singh

Goutham Vasam

Rahul Pawar

Yagna P R Jarajapu

Affiliations

Soon will be listed here.

Abstract

Introduction: Angiotensin (Ang)-(1-7) is a recently identified vasoprotective heptapeptide, and it appears to activate the reparative functions of bone marrow-derived stem/progenitor cells (BMPCs).

Aim: This study evaluated the effect of Ang-(1-7) in the angiogenic function of cavernosum in type 1 diabetes (T1D) and delineated the role of BMPCs in this protective function.

Methods: T1D was induced by streptozotocin in mice, and mice with 20-24 weeks of diabetes were used for the study. Ang-(1-7) was administered subcutaneously by using osmotic pumps. Cavernosa, and BMPCs from peripheral blood and bone marrow were evaluated in different assay systems.

Main Outcome Measures: Angiogenic function was determined by endothelial tube formation in matrigel assay. Circulating BMPCs were enumerated by flow cytometry and proliferation was determined by BrdU incorporation. Cell-free supernatant of BMPCs were collected and tested for paracrine angiogenic effect. Expression of angiogenic factors in BMPCs and cavernosa were determined by real-time polymerase chain reaction.

Results: Ang-(1-7) (100 nM) stimulated angiogenesis in mouse cavernosum that was partially inhibited by Mas1 receptor antagonist, A779 (10 μM) (P < 0.05). In cavernosa of T1D, the angiogenic responses to Ang-(1-7) (P < 0.005) and VEGF (100 nM) (P < 0.03) were diminished. Ang-(1-7) treatment for 4 weeks reversed T1D-induced decrease in the VEGF-mediated angiogenesis. Ang-(1-7) treatment increased the circulating number of BMPCs and proliferation that were decreased in T1D (P < 0.02). Paracrine angiogenic function of BMPCs was reduced in diabetic BMPCs, which was reversed by Ang-(1-7). In diabetic BMPCs, SDF and angiopoietin-1 were upregulated by Ang-(1-7), and in cavernosum, VEGFR1, Tie-2, and SDF were upregulated and angiopoietin-2 was down-regulated.

Conclusions: Ang-(1-7) stimulates angiogenic function of cavernosum in diabetes via its stimulating effects on both cavernosal microvasculature and BMPCs.

Citing Articles

Restoration of the gut barrier integrity and restructuring of the gut microbiome in aging by angiotensin-(1-7).

Chittimalli K, Jahan J, Sakamuri A, McAdams Z, Ericsson A, Jarajapu Y Clin Sci (Lond). 2023; 137(11):913-930.

PMID: 37254732 PMC: 10881191. DOI: 10.1042/CS20220904.

ACE2/ACE imbalance and impaired vasoreparative functions of stem/progenitor cells in aging.

Joshi S, Chittimalli K, Jahan J, Vasam G, Jarajapu Y Geroscience. 2020; 43(3):1423-1436.

PMID: 33247425 PMC: 7694587. DOI: 10.1007/s11357-020-00306-w.

Targeting Angiotensin-Converting Enzyme-2/Angiotensin-(1-7)/Mas Receptor Axis in the Vascular Progenitor Cells for Cardiovascular Diseases.

Jarajapu Y Mol Pharmacol. 2020; 99(1):29-38.

PMID: 32321734 PMC: 7725063. DOI: 10.1124/mol.119.117580.

The role of receptor MAS in microglia-driven retinal vascular development.

Foulquier S, Caolo V, Swennen G, Milanova I, Reinhold S, Recarti C Angiogenesis. 2019; 22(4):481-489.

PMID: 31240418 PMC: 6863789. DOI: 10.1007/s10456-019-09671-3.

Mechanisms of Mas1 Receptor-Mediated Signaling in the Vascular Endothelium.

Hoffmann B, Stodola T, Wagner J, Didier D, Exner E, Lombard J Arterioscler Thromb Vasc Biol. 2017; 37(3):433-445.

PMID: 28082260 PMC: 5323371. DOI: 10.1161/ATVBAHA.116.307787.

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