Deletion of Superoxide Dismutase 1 Blunted Inflammatory Aortic Remodeling in Hypertensive Mice under Angiotensin II Infusion.

Yasunaga Shiraishi,Yasuo Ido,Masanori Fujita,Takehiko Kujiraoka,Norio Ishigami,Takeshi Adachi,Atsushi Sato

doi:10.3390/antiox10030471

Yasunaga Shiraishi, Yasuo Ido + Show 5 more

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https://doi.org/10.3390/antiox10030471

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Abstract

Superoxide dismutase (SOD) is an enzyme that catalyzes the dismutation of two superoxide anions (O2·−) into hydrogen peroxide (H2O2) and oxygen (O2) and is generally known to protect against oxidative stress. Angiotensin II (AngII) causes vascular hypertrophic remodeling which is associated with H2O2 generation. The aim of this study is to investigate the role of cytosolic SOD (SOD1) in AngII-induced vascular hypertrophy. We employed C57/BL6 mice (WT) and SOD1 deficient mice (SOD1−/−) with the same background. They received a continuous infusion of saline or AngII (3.2 mg/kg/day) for seven days. The blood pressures were equally elevated at 1.5 times with AngII, however, vascular hypertrophy was blunted in SOD1−/− mice compared to WT mice (WT mice 91.9 ± 1.13 µm versus SOD1−/− mice 68.4 ± 1.41 µm p < 0.001). The elevation of aortic interleukin 6 (IL-6) and phosphorylation of pro-inflammatory STAT3 due to AngII were also blunted in SOD1−/− mice’s aortas. In cultured rat vascular smooth muscle cells (VSMCs), reducing expression of SOD1 with siRNA decreased AngII induced IL-6 release as well as phosphorylation of STAT3. Pre-incubation with polyethylene glycol (PEG)-catalase also attenuated phosphorylation of STAT3 due to AngII. These results indicate that SOD1 in VSMCs plays a role in vascular hypertrophy due to increased inflammation caused by AngII, probably via the production of cytosolic H2O2.

Highlights

In our bodies, the reactive oxygen species (ROSs) are constantly produced, and they are high reactivity which potentially damages the biological systems
With down-regulation of SOD1, STAT3 phosphorylation due to incubation with interleukin 6 (IL-6) was blunted (Figure 6E). These results suggest that SOD1 is involved in IL-6 secretion from vascular smooth muscle cells (VSMCs) and phosphorylation of STAT3 by IL-6 in the presence of Angiotensin II (AngII)
We examined the role of SOD1 in vascular physiology and pathophysiology using a well-characterized SOD1 knockout mouse, in particular focusing on aortic hypertrophy and inflammation

Summary

Introduction

The reactive oxygen species (ROSs) are constantly produced, and they are high reactivity which potentially damages the biological systems. An appropriate amount of ROSs is necessary for biological processes including cell signaling [1,2] and defense system. The proper balance of pro-oxidant-antioxidant system maintains biological homeostasis [3]. Perturbing this balance leads to oxidative stress and causes many disorders including vascular diseases. Angiotensin II (AngII) is the established pathophysiology of hypertension and vascular hypertrophy. Part of this pathophysiology is caused by ROSs produced by NADPH oxidase (NOX) [4,5]. Some NOXs localize at specific subcellular compartments such as caveolae and endosomes [11] and the produced O2 ·−

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