The susceptibility of bioprosthetic heart valve leaflets to oxidation.

The susceptibility of bioprosthetic heart valve leaflets to oxidation.
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DOI:
10.1016/j.biomaterials.2013.11.045
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发表时间:
2014-02
期刊:
影响因子:
14
通讯作者:
Levy, Robert J.
Levy, Robert J.
中科院分区:
工程技术1区
文献类型:
--
作者:
Christian, Abigail J.;Lin, Hongqiao;Alferiev, Ivan S.;Connolly, Jeanne M.;Ferrari, Giovanni;Hazen, Stanley L.;Ischiropoulos, Harry;Levy, Robert J.

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生物心脏瓣膜(BHV)瓣叶结构退化导致器械失效,限制了BHV的临床应用。在这项研究中,我们调查的假设,氧化应激有助于这一过程。使用质谱法分析了因器械失效而取出的15例临床BHV的氧化氨基酸。与未植入的BHV材料戊二醛处理的牛心包(BP)相比,临床BHV外植体中的邻酪氨酸、间酪氨酸和二酪氨酸水平显著升高。BP在体外暴露于氧化条件(FeSO 4/H2 O2),以评估氧化对结构退化的影响。暴露于氧化条件导致胶原蛋白显著退化、戊二醛交联损失和对胶原酶降解的敏感性增加。通过共价连接氧化剂清除剂3-(4-羟基-3,5-二叔丁基苯基)丙胺(DBP)改性的BP对氧化诱导的结构损伤的所有监测参数具有抗性。这些结果表明,氧化应激,特别是通过羟基自由基和酪氨酰自由基介导的途径,可能参与BHV的结构变性,并且这种机制可以通过局部递送抗氧化剂如DBP来减弱。
The clinical use of bioprosthetic heart valves (BHV) is limited due to device failure caused by structural degeneration of BHV leaflets. In this study we investigated the hypothesis that oxidative stress contributes to this process. Fifteen clinical BHV that had been removed for device failure were analyzed for oxidized amino acids using mass spectrometry. Significantly increased levels of ortho-tyrosine, meta-tyrosine and dityrosine were present in clinical BHV explants as compared to the non-implanted BHV material glutaraldehyde treated bovine pericardium (BP). BP was exposed in vitro to oxidizing conditions (FeSO4/H2O2) to assess the effects of oxidation on structural degeneration. Exposure to oxidizing conditions resulted in significant collagen deterioration, loss of glutaraldehyde cross-links, and increased susceptibility to collagenase degradation. BP modified through covalent attachment of the oxidant scavenger 3-(4-hydroxy-3,5-di-tert-butylphenyl) propyl amine (DBP) was resistant to all of the monitored parameters of structural damage induced by oxidation. These results indicate that oxidative stress, particularly via hydroxyl radical and tyrosyl radical mediated pathways, may be involved in the structural degeneration of BHV, and that this mechanism may be attenuated through local delivery of antioxidants such as DBP.
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