TGF-β Neutralization Enhances AngII-Induced Aortic Rupture and Aneurysm in Both Thoracic and Abdominal Regions

Authors

Xiaofeng Chen, University of KentuckyFollow
Debra L. Rateri, University of KentuckyFollow
Deborah A. Howatt, University of KentuckyFollow
Anju Balakrishnan, University of KentuckyFollow
Jessica J. Moorleghen, University of KentuckyFollow
Lisa A. Cassis, University of KentuckyFollow
Alan Daugherty, University of KentuckyFollow

Abstract

AngII and TGF-β interact in development of thoracic and abdominal aortic diseases, although there are many facets of this interaction that have not been clearly defined. The aim of the present study was to determine the effects of TGF-β neutralization on AngII induced-aortic pathologies. Male C57BL/6J mice were administered with either a rabbit or mouse TGF-β neutralizing antibody and then infused with AngII. The rabbit TGF-β antibody modestly reduced serum TGF-β concentrations, with no significant enhancements to AngII-induced aneurysm or rupture. Administration of this rabbit TGF-β antibody in mice led to high serum titers against rabbit IgG that may have attenuated the neutralization. In contrast, a mouse TGF-β antibody (1D11) significantly increased rupture in both the ascending and suprarenal aortic regions, but only at doses that markedly decreased serum TGF-β concentrations. High doses of 1D11 antibody significantly increased AngII-induced ascending and suprarenal aortic dilatation. To determine whether TGF-β neutralization had effects in mice previously infused with AngII, the 1D11 antibody was injected into mice that had been infused with AngII for 28 days and were observed during continued infusion for a further 28 days. Despite near ablations of serum TGF-β concentrations, the mouse TGF-β antibody had no effect on aortic rupture or dimensions in either ascending or suprarenal region. These data provide further evidence that AngII-induced aortic rupture is enhanced greatly by TGF-β neutralization when initiated before pathogenesis.

Document Type

Article

Publication Date

4-22-2016

Notes/Citation Information

Published in PLOS ONE, v. 11, no. 4, e0153811, p. 1-16.

© 2016 Chen et al.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Digital Object Identifier (DOI)

https://doi.org/10.1371/journal.pone.0153811

Funding Information

National Marfan Foundation: http://www.marfan.org/?gclid=CNKUmZ3frMoCFYwvgQodAqMGTQ, National Institutes of Health - HL 107319 http://www.nih.gov/.

Repository Citation

Chen, Xiaofeng; Rateri, Debra L.; Howatt, Deborah A.; Balakrishnan, Anju; Moorleghen, Jessica J.; Cassis, Lisa A.; and Daugherty, Alan, "TGF-β Neutralization Enhances AngII-Induced Aortic Rupture and Aneurysm in Both Thoracic and Abdominal Regions" (2016). Saha Cardiovascular Research Center Faculty Publications. 29.
https://uknowledge.uky.edu/cvrc_facpub/29