Superoxide in calcified regions of stenotic human aortic valves

• Published in: The FASEB journal 2007-04, Vol.21 (5), p.A446-A446
• Main Authors: Miller, Jordan D, Lund, Donald D, Serrano, Kristine M, Chu, Yi, Weiss, Robert M, Brooks, Robert M, Richenbacher, Wayne E, Pena‐Silva, Ricardo A, Everett, Jeffrey E, Heistad, Donald D
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.21.5.A446-c

Oxidative stress is evident in atherosclerotic plaques. We tested the hypothesis that oxidative stress is increased in calcific aortic valve stenosis (AVS). Superoxide levels were measured in explanted aortic valves from humans with AVS (n = 19) and non‐calcified valves from donor hearts rejected for transplantation (n = 14). Superoxide levels (using the Tiron‐inhibitable fraction of lucigenin‐enhanced chemiluminescence) were higher in heavily calcified AVS tissue (2.9 ± 0.4 RLU/sec/mm2, mean ± SE) than donor tissue (0.9 ± 0.2 RLU/sec/mm2, p < 0.01) or non‐calcified regions of AVS valves (1.2 ± 0.2 RLU/sec/mm2, p < 0.01). Images acquired using confocal microscopy also showed that superoxide (dihydroethidium fluorescence) was elevated near calcified regions of the valve. Quantitative real‐time RT‐PCR showed no changes in nox2 or nox4 expression in calcified regions versus non‐calcified regions. However, expression of extracellular superoxide dismutase (SOD) and copper zinc SOD were reduced in calcified regions. In homogenized valve tissue, NADPH oxidase activity was similar in calcified and noncalcified valve regions, but total SOD activity was reduced by ~50% in calcified regions. In conclusion, superoxide is increased specifically near calcified regions of stenotic human valves through a mechanism that may involve loss of antioxidant mechanisms.