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

• Main Authors: Yasunaga Shiraishi (Author), Norio Ishigami (Author), Takehiko Kujiraoka (Author), Atsushi Sato (Author), Masanori Fujita (Author), Yasuo Ido (Author), Takeshi Adachi (Author)
• Format: Book
• Published: MDPI AG, 2021-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 <i>p</i> < 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.

Item Description

10.3390/antiox10030471
2076-3921