Nitrite-induced cross-linking alters remodeling and mechanical properties of collagenous engineered tissues.
Nitrite-induced cross-linking alters remodeling and mechanical properties of collagenous engineered tissues.
复制标题
亚硝酸盐诱导的交联改变胶原工程组织的重塑和机械性能。
DOI：
10.1080/03008200600721569
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Holmes,JeffreyW
中科院分区：
文献类型：
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作者：
Paik,DavidC;Saito,LynneY;Sugirtharaj,DorcasD;Holmes,JeffreyW
对长寿结缔组织蛋白的累积损伤在与年龄相关的人类疾病（例如心血管硬化和年龄相关性黄斑变性）的发展中发挥着关键作用。导致越来越不溶性、不可消化的受损胶原蛋白积累的过程仅部分已知。非酶糖基化（NEG）就是这样一个过程，并与糖尿病相关并发症和衰老的发展有关。另外一种与吸烟和炎症相关疾病特别相关的新机制涉及结缔组织蛋白的非酶亚硝酸盐（NEN）修饰。本研究旨在探讨纤维状I型胶原NEN对胶原组织细胞介导的重塑和力学性能的影响。使用我们实验室开发的体外成纤维细胞填充的胶原蛋白凝胶模型系统的修改，我们测试了两个假设：NEN降低了原代成人心脏成纤维细胞重塑I型胶原蛋白凝胶的能力; NEN降低了I型胶原蛋白凝胶的变形性进行机械测试。结果表明，NEN损害胶原工程组织中细胞介导的重塑和机械变形能力。此外，这些机械变化与通过SDS-PAGE测定的交联程度相关。因此，我们得出结论，NEN反应可能导致含胶原组织的生物力学特性改变，这与在人类疾病中观察到的年龄相关功能下降一致。
Cumulative damage to long-lived connective tissue proteins play a key role in the development of age-related human diseases such as cardiovascular stiffening and age-related macular degeneration. The processes that result in the accumulation of increasingly insoluble, undigestible damaged collagen are only partially known. Nonenzymatic glycation (NEG) is one such process and has been linked to the development of diabetic-related complications and aging. An additional novel mechanism particularly relevant to smoking- and inflammation-related diseases involves the nonenzymatic nitrite (NEN) modification of connective tissue proteins. The present study was undertaken to examine the effects of NEN of fibrillar type I collagen on cell-mediated remodeling and mechanical properties of collagenous tissues. Using a modification of anin vitrofibroblast-populated collagen gel model system developed in our laboratory, we tested two hypotheses: NEN reduces the ability of primary adult cardiac fibroblasts to remodel type I collagen gels; NEN reduces the deformability of type I collagen gels subjected to mechanical testing. The results show that NEN impairs both cell-mediated remodeling and mechanical deformability in collagenous engineered tissues. Furthermore, these mechanical changes correlate with the degree of cross-linking as determined by SDS-PAGE. Thus, we concluded that NEN reactions may contribute to alterations in the biomechanical properties of collagen-containing tissues consistent with the age-related functional decline observed in human disease.