Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel
Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel
复制标题
DOI：
10.1016/j.biomaterials.2016.06.060
复制
发表时间：
2016-10-01
期刊：
影响因子：
14
通讯作者：
Chiou, Shih-Hwa
中科院分区：
文献类型：
--
作者：
Cheng, Yung-Hsin;Lin, Feng-Huei;Chiou, Shih-Hwa
衰老相关的氧化应激被认为是心血管疾病（CVD）的主要危险因素，可能与线粒体功能障碍和活性氧（ROS）过量产生有关。 Cisd2是一种线粒体外膜蛋白，在控制哺乳动物的寿命中发挥着重要作用。阿魏酸（FA）是一种天然抗氧化剂，能够改善心血管功能并抑制CVD致病过程。然而，由于稳定性和生物利用度问题，直接使用抗氧化剂分子进行治疗具有挑战性。在本研究中，使用含有FA的热敏壳聚糖-明胶基水凝胶来处理氧化应激下源自Cisd2(-/-)小鼠诱导多能干细胞的Cisd2缺陷(Cisd2(-/-))心肌细胞(CM)。结果表明，所开发的水凝胶可以持续释放 FA 并提高细胞活力。负载 FA 的水凝胶的后处理通过增加过氧化氢酶活性和减少内源性活性氧 (ROS) 产生，有效减少了 Cisd2(-/-) CM 中氧化应激诱导的损伤。 FA负载水凝胶的体内生物相容性在皮下注射的兔子和心肌内注射的Cisd2(-/-)小鼠中得到证实。这些结果表明，热敏FA负载水凝胶可以挽救Cisd2(-/-) CM免受氧化应激引起的损伤，并可能在未来CVD治疗中具有潜在应用。 (C) 2016 Elsevier Ltd. 保留所有权利。
Aging-related oxidative stress is considered a major risk factor of cardiovascular diseases (CVD) and could be associated with mitochondrial dysfunction and reactive oxygen species (ROS) overproduction. Cisd2 is an outer mitochondrial membrane protein and plays an important role in controlling the lifespan of mammals. Ferulic acid (FA), a natural antioxidant, is able to improve cardiovascular functions and inhibit the pathogenetic CVD process. However, directly administering therapeutics with antioxidant molecules is challenging because of stability and bioavailability issues. In the present study, thermosensitive chitosan-gelatin-based hydrogel containing FA was used to treat Cisd2-deficient (Cisd2(-/-)) cardiomyocytes (CM) derived from induced pluripotent stem cells of Cisd2(-/-) murine under oxidative stress. The results revealed that the developed hydrogel could provide a sustained release of FA and increase the cell viability. Post-treatment of FA-loaded hydrogel effectively decreased the oxidative stress-induced damage in Cisd2(-/-) CM via increasing catalase activity and decreasing endogenous reactive oxygen species (ROS) production. The in vivo biocompatibility of FA-loaded hydrogel was confirmed in subcutaneously injected rabbits and intramyocardially injected Cisd2(-/-) mice. These results suggest that the thermosensitive FA-loaded hydrogel could rescue Cisd2(-/-) CM from oxidative stress-induced damage and may have potential applications in the future treatment of CVD. (C) 2016 Elsevier Ltd. All rights reserved.