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

被引：58
作者：
Chen, Xiaofeng [1 ,2 ]
Rateri, Debra L. [2 ]
Howatt, Deborah A. [2 ]
Balakrishnan, Anju [2 ]
Moorleghen, Jessica J. [2 ]
Cassis, Lisa A. [3 ]
Daugherty, Alan [2 ,4 ]
机构：
[1] Wenzhou Med Univ, Taizhou Hosp, Dept Cardiol, Lab Cardiovasc Dis, Wenzhou, Zhejiang, Peoples R China
[2] Univ Kentucky, Saha Cardiovasc Res Ctr, Lexington, KY USA
[3] Univ Kentucky, Dept Pharmacol & Nutr Sci, Lexington, KY USA
[4] Univ Kentucky, Dept Physiol, Lexington, KY USA
来源：
PLOS ONE | 2016年 / 11卷 / 04期
基金：
美国国家卫生研究院;
关键词：
ANGIOTENSIN-II; GROWTH; RECEPTOR; HYPERPLASIA; ATHEROSCLEROSIS; HYPERTROPHY; PROGRESSION; DISRUPTION; EXPRESSION; GAMMA;
D O I：
10.1371/journal.pone.0153811
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
AngII and TGF-beta 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-beta neutralization on AngII induced-aortic pathologies. Male C57BL/6J mice were administered with either a rabbit or mouse TGF-beta neutralizing antibody and then infused with AngII. The rabbit TGF-beta antibody modestly reduced serum TGF-beta concentrations, with no significant enhancements to AngII-induced aneurysm or rupture. Administration of this rabbit TGF-beta antibody in mice led to high serum titers against rabbit IgG that may have attenuated the neutralization. In contrast, a mouse TGF-beta antibody (1D11) significantly increased rupture in both the ascending and suprarenal aortic regions, but only at doses that markedly decreased serum TGF-beta concentrations. High doses of 1D11 antibody significantly increased AngII-induced ascending and suprarenal aortic dilatation. To determine whether TGF-beta 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-beta concentrations, the mouse TGF-beta 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-beta neutralization when initiated before pathogenesis.
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页数：16
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