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

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.

Abstract 334: Complementary Atherosclerosis Prophylaxis in Patients After Coronary Bypass Surgery

Background and purpose: Atherosclerotic coronary arteries can be well-treated with innovative medicaments, through PCI or by aortocoronary bypasses. Some of the stents and bypasses close again in spite of blood-thinning. We examined in a clinical pilot study of 8 patients who had undergone a CABG operation whether atherosclerosis prophylaxis can be practised through an additional phytochemical approach with ginkgo (EGb 761, 2 × 120 mg/d). Furthermore, our trial aimed to inquire whether the bypasses remain open. Methods: As a biomarker for plaque development, atherosclerotic nanoplaque formation and size were monitored by laser ellipsometry (patent EP 0 946 876). Lipoproteins, cytosolic SOD, oxLDL, and [cAMP] and [cGMP] were determined by established methods. Results: After 2-month medication, the decrease in nanoplaque formation amounted to 11.9 ± 2.5% (p < 0.01) and in nanoplaque size to 24.4 ± 8.1% (p < 0.02), after 5 years 25.0 ± 3.7% (p < 0.01) and 45.8 ± 9.5% (p < 0.01), respectively. A multiple correlation between nanoplaque reduction and the risk factors oxLDL/LDL, Lp(a) and cGMP yielded an estimate of their relative contribution to nanoplaque diminution (34.7%, 43.3%, 22.0%). In the 5 year follow-up examination using high-resolution CT, all arterial and 86.7% of the venous bypasses were open, whereby the increase in blood nucleotides seemed to have played a prominent role. Conclusion: Ginkgo may be used as complementary drug with potentially preventive character after coronary-artery bypass graft.

Induction of Manganese-Containing Superoxide Dismutase Is Required for Acid Tolerance in Vibrio vulnificus

ABSTRACT The manganese-containing superoxide dismutase (MnSOD) of Vibrio vulnificus, normally detected after the onset of the stationary phase, is expressed during the lag that immediately follows the transfer of cells grown exponentially to a fresh medium acidified to pH 5.0, whereas Fe-containing SOD is constitutively expressed. The signal triggering the growth lag and MnSOD induction therein is not low pH but intracellular superoxide accumulated under these conditions, since addition of a superoxide scavenger not only shortened the lag but also abrogated the MnSOD induction. If the lysine decarboxylase reaction proceeds in the presence of sufficient lysine, the broth is rapidly neutralized to abolish the generation of oxidative stress. Accordingly, the acid tolerance response was examined without the addition of lysine. SoxR regulates MnSOD induction. Lack of MnSOD caused by mutations in soxR or sodA resulted in low tolerance to low pH. The fur mutant derepressing MnSOD showed better tolerance than the wild type. Thus, an increase in total cytosolic SOD activity through MnSOD induction is essential for the cell to withstand the acid challenge. The contribution of cuprozinc-containing SOD to acid tolerance is not significant compared with those of cytosolic SODs.