Dysregulation of antioxidant mechanisms contributes to increased oxidative stress in calcific aortic valvular stenosis in humans.
Dysregulation of antioxidant mechanisms contributes to increased oxidative stress in calcific aortic valvular stenosis in humans.
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DOI：
10.1016/j.jacc.2008.05.043
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发表时间：
2008-09-02
影响因子：
24
通讯作者：
Heistad, Donald D.
中科院分区：
文献类型：
--
作者：
Miller, Jordan D.;Chu, Yi;Brooks, Robert M.;Richenbacher, Wayne E.;Pena-Silva, Ricardo;Heistad, Donald D.
这项研究的目的是确定钙化、狭窄的主动脉瓣中氧化应激是否增加，并检查可能导致氧化应激增加的机制。氧化应激在动脉粥样硬化病变中增加，并可能在斑块进展和钙化中发挥重要作用。氧化应激在瓣膜疾病中的作用尚不清楚。对不适合移植的心脏瓣膜和手术切除的狭窄主动脉瓣的正常瓣膜进行了超氧化物歧化(二氢乙锭荧光和光亮素增强的化学发光)、过氧化氢(H_2O_2)(二氯荧光素荧光)以及前、抗氧化酶的表达和活性的测定。在正常瓣膜中，超氧化物水平相对较低，并且均匀分布在整个瓣膜中。在狭窄瓣膜中，瓣膜钙化区域附近的超氧化物水平增加了2倍(p<；0.05)；非钙化区域与正常瓣膜没有显著差异。狭窄瓣膜钙化区域的过氧化氢水平也显著升高。狭窄瓣膜钙化区的烟酰胺腺嘌呤二核苷酸磷酸氧化酶活性未见升高。通过抑制一氧化氮合酶(NOS)，狭窄瓣膜中的超氧化物水平显著降低，这表明该酶是解偶联的。主动脉瓣钙化部位的抗氧化机制减弱，因为总超氧化物歧化酶活性和3种超氧化物歧化酶亚型的表达均显著降低。在钙化周围区域，过氧化氢酶的表达也降低。这项研究首次提供了人类主动脉瓣狭窄钙化区域氧化应激增加的证据。氧化应激的增加至少部分是由于抗氧化酶的表达和活性的减少，或许是由于解偶联的NOS活性。因此，在狭窄的主动脉瓣和动脉粥样硬化的动脉中，氧化应激的机制有很大不同。
The aim of this study was to determine whether oxidative stress is increased in calcified, stenotic aortic valves and to examine mechanisms that might contribute to increased oxidative stress. Oxidative stress is increased in atherosclerotic lesions and might play an important role in plaque progression and calcification. The role of oxidative stress in valve disease is not clear. Superoxide (dihydroethidium fluorescence and lucigenin-enhanced chemiluminescence), hydrogen peroxide (H2O2) (dichlorofluorescein fluorescence), and expression and activity of pro- and anti-oxidant enzymes were measured in normal valves from hearts not suitable for transplantation and stenotic aortic valves that were removed during surgical replacement of the valve. In normal valves, superoxide levels were relatively low and distributed homogeneously throughout the valve. In stenotic valves, superoxide levels were increased 2-fold near the calcified regions of the valve (p < 0.05); noncalcified regions did not differ significantly from normal valves. Hydrogen peroxide levels were also markedly elevated in calcified regions of stenotic valves. Nicotinamide adenine dinucleotide phosphate oxidase activity was not increased in calcified regions of stenotic valves. Superoxide levels in stenotic valves were significantly reduced by inhibition of nitric oxide synthases (NOS), which suggests uncoupling of the enzyme. Antioxidant mechanisms were reduced in calcified regions of the aortic valve, because total superoxide dismutase (SOD) activity and expression of all 3 SOD isoforms was significantly decreased. Catalase expression also was reduced in pericalcific regions. This study provides the first evidence that oxidative stress is increased in calcified regions of stenotic aortic valves from humans. Increased oxidative stress is due at least in part to reduction in expression and activity of antioxidant enzymes and perhaps to uncoupled NOS activity. Thus, mechanisms of oxidative stress differ greatly between stenotic aortic valves and atherosclerotic arteries.
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影响因子：
37.8
作者：
Antoniades, Charalambos;Shirodaria, Cheerag;Channon, Keith M.
通讯作者：
Channon, Keith M.
DOI：
10.1161/01.atv.0000255952.47980.c2
发表时间：
2007-03-01
影响因子：
8.7
作者：
Messika-Zeitoun, David;Bielak, Lawrence F.;Enriquez-Sarano, Maurice
通讯作者：
Enriquez-Sarano, Maurice
影响因子：
15.9
作者：
Landmesser, U;Dikalov, S;Harrison, DG
通讯作者：
Harrison, DG
影响因子：
4.8
作者：
Kuzkaya, N;Weissmann, N;Dikalov, S
通讯作者：
Dikalov, S
影响因子：
4.6
作者：
Jian, B;Narula, N;Levy, RJ
通讯作者：
Levy, RJ