Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel

Yung-Hsin Cheng; Feng-Huei Lin; Chien-Ying Wang; Chen-Yuan Hsiao; Hung-Ching Chen; Hsin-Yu Kuo; Ting-Fen Tsai; Shih-Hwa Chiou

doi:10.1016/j.biomaterials.2016.06.060

Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel

Biomaterials. 2016 Oct:103:207-218. doi: 10.1016/j.biomaterials.2016.06.060. Epub 2016 Jun 28.

Authors

Yung-Hsin Cheng¹, Feng-Huei Lin², Chien-Ying Wang³, Chen-Yuan Hsiao⁴, Hung-Ching Chen⁵, Hsin-Yu Kuo⁶, Ting-Fen Tsai⁷, Shih-Hwa Chiou⁸

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ 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.
⁸ 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.

PMID: 27392289
DOI: 10.1016/j.biomaterials.2016.06.060

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.

Keywords: Chitosan; Cisd2; Ferulic acid; Hydrogel; Mitochondria.

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
Antioxidants / administration & dosage
Autophagy-Related Proteins
Carrier Proteins / metabolism*
Cells, Cultured
Coumaric Acids / administration & dosage*
Coumaric Acids / chemistry
Delayed-Action Preparations / administration & dosage*
Delayed-Action Preparations / chemistry
Hydrogels / administration & dosage
Hydrogels / chemistry
Injections
Mice
Mice, Knockout
Myocytes, Cardiac / drug effects*
Myocytes, Cardiac / physiology*
Nerve Tissue Proteins / metabolism*
Oxidative Stress / drug effects*
Oxidative Stress / physiology
Reactive Oxygen Species / metabolism

Substances

Anti-Inflammatory Agents, Non-Steroidal
Antioxidants
Autophagy-Related Proteins
Carrier Proteins
Coumaric Acids
Delayed-Action Preparations
Hydrogels
Nerve Tissue Proteins
Noxp70 protein, mouse
Reactive Oxygen Species
ferulic acid