Model studies of advanced glycation end product modification of heterograft biomaterials: The effects of in vitro glucose, glyoxal, and serum albumin on collagen structure and mechanical properties.
Model studies of advanced glycation end product modification of heterograft biomaterials: The effects of in vitro glucose, glyoxal, and serum albumin on collagen structure and mechanical properties.
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DOI：
10.1016/j.actbio.2020.12.053
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发表时间：
2021-03-15
影响因子：
9.7
通讯作者：
Levy RJ
中科院分区：
文献类型：
--
作者：
Rock CA;Keeney S;Zakharchenko A;Takano H;Spiegel DA;Krieger AM;Ferrari G;Levy RJ
戊二醛交联异种移植组织，牛心包（BP）或猪主动脉瓣，是用于心脏瓣膜疾病的心脏外科手术的生物人工心脏瓣膜（BHV）的小叶材料。由于结构性瓣膜变性（SVD），通常伴有钙化，BHV失效。晚期糖基化终产物（AGE）是翻译后糖还原蛋白的非酶反应产物。AGE在SVD-BHV临床移植体中存在，在未植入的BHV中未检测到。先前的研究在体外用葡萄糖分解产物乙二醛和血清白蛋白模拟BP-AGE的形成。然而，葡萄糖是最丰富的AGE前体。因此，本研究探讨了BHV对葡萄糖相关AGE的易感性，以及血清蛋白导致胶原结构和力学性能恶化的假设。体外实验研究了14c -葡萄糖和14c -乙二醛添加和不添加牛血清白蛋白（BSA）对BP和猪胶原海绵（CS） AGE形成的影响。葡萄糖掺入水平显著低于乙二醛（p<0.02）。BSA共孵育显示BP和CS对乙二醛和葡萄糖的摄取减少。BSA孵育导致BP质量显著增加，乙二醛共孵育增强了BP质量。BP双光子显微镜显示，BSA诱导的胶原结构破坏在葡萄糖或乙二醛共孵育时更为严重。CS的单轴测试表明，与对照组相比，葡萄糖或乙二醛与BSA一起导致粘弹性松弛加速恶化，并且在28天的时间过程中增加了刚度。总之，葡萄糖、乙二醛和牛血清白蛋白是age介导的异源胶原结构破坏和力学性能恶化的唯一原因。
Glutaraldehyde cross-linked heterograft tissues, bovine pericardium (BP) or porcine aortic valves, are the leaflet materials in bioprosthetic heart valves (BHV) used in cardiac surgery for heart valve disease. BHV fail due to structural valve degeneration (SVD), often with calcification. Advanced glycation end products (AGE) are post-translational, non-enzymatic reaction products from sugars reducing proteins. AGE are present in SVD-BHV clinical explants and are not detectable in un-implanted BHV. Prior studies modeled BP-AGE formation in vitro with glyoxal, a glucose breakdown product, and serum albumin. However, glucose is the most abundant AGE precursor. Thus, the present studies investigated the hypothesis that BHV susceptibility to glucose related AGE, together with serum proteins, results in deterioration of collagen structure and mechanical properties. In vitro experiments studied AGE formation in BP and porcine collagen sponges (CS) comparing 14C-glucose and 14C-glyoxal with and without bovine serum albumin (BSA). Glucose incorporation occurred at a significantly lower level than glyoxal (p<0.02). BSA co-incubations demonstrated reduced glyoxal and glucose uptake by both BP and CS. BSA incubation caused a significant increase in BP mass, enhanced by glyoxal co-incubation. Two-photon microscopy of BP showed BSA induced disruption of collagen structure that was more severe with glucose or glyoxal co-incubation. Uniaxial testing of CS demonstrated that glucose or glyoxal together with BSA compared to controls, caused accelerated deterioration of viscoelastic relaxation, and increased stiffness over a 28-day time course. In conclusion, glucose, glyoxal and BSA uniquely contribute to AGE-mediated disruption of heterograft collagen structure and deterioration of mechanical properties.
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