title: Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel.
abstract: 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.
authors.affiliation: Department of Education and Research, Taipei City Hospital, No. 145, Zhengzhou Rd., Datong Dist., Taipei, 103, Taiwan, ROC; Institute of Pharmacology, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, 112, Taiwan, ROC. Electronic address: yunghsin@ym.edu.tw.
authors.forename: Yung-Hsin
authors.initials: YH
authors.lastname: Cheng
authors.affiliation: Institute of Biomedical Engineering, College of Engineering and College of Medicine, National Taiwan University, No. 1, Jen Ai Rd., Sec. 1, Taipei, 100, Taiwan, ROC; Institute of Biomedical Engineering and Nanomedicine, National Health Research Institute, No. 35, Keyan Rd., Miaoli, 350, Taiwan, ROC. Electronic address: double@ntu.edu.tw.
authors.forename: Feng-Huei
authors.initials: FH
authors.lastname: Lin
authors.affiliation: Emergency Department, Taipei Veterans General Hospital, No. 201, Shipai Rd., Sec. 2, Taipei, 112, Taiwan, ROC; National Yang-Ming University School of Medicine, No. 155, Linong Street, Sec. 2, Taipei, 112, Taiwan, ROC. Electronic address: wangcy@vghtpe.gov.tw.
authors.forename: Chien-Ying
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Surgery, National Yang-Ming University Hospital, No. 152, Xinmin Rd., Yilan, 260, Taiwan, ROC; Graduate Institute of Medical Sciences, National Defense Medical Center, No. 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei, 114, Taiwan, ROC. Electronic address: dreamsoar2005@gmail.com.
authors.forename: Chen-Yuan
authors.initials: CY
authors.lastname: Hsiao
authors.affiliation: Institute of Pharmacology, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, 112, Taiwan, ROC. Electronic address: a12208@hotmail.com.
authors.forename: Hung-Ching
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Institute of Pharmacology, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, 112, Taiwan, ROC. Electronic address: hsinyu780302@gmail.com.
authors.forename: Hsin-Yu
authors.initials: HY
authors.lastname: Kuo
authors.affiliation: Department of Life Sciences & Institute of Genome Sciences, National Yang-Ming University, No.155, Linong Street, Sec. 2, Taipei, 112, Taiwan, ROC. Electronic address: tftsai@ym.edu.tw.
authors.forename: Ting-Fen
authors.initials: TF
authors.lastname: Tsai
authors.affiliation: Institute of Pharmacology, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, 112, Taiwan, ROC; Department of Medical Research, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei, 112, Taiwan, ROC; Genomics Research Center, Academia Sinica, No. 128 Academia Road, Section 2, Taipei, 115, Taiwan, ROC. Electronic address: shchiou@vghtpe.gov.tw.
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D000975:Antioxidants / Q000008:administration & dosage; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003373:Coumaric Acids / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry; D007267:Injections; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D003373:Coumaric Acids; D003692:Delayed-Action Preparations; D020100:Hydrogels; D009419:Nerve Tissue Proteins; C515811:Noxp70 protein, mouse; D017382:Reactive Oxygen Species; C004999:ferulic acid
keywords: Chitosan; Cisd2; Ferulic acid; Hydrogel; Mitochondria