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AAV9-Mediated Cardiac CNTF Overexpression Exacerbated Adverse Cardiac Remodeling in Streptozotocin-Induced Type 1 Diabetic Models

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A Correction to this article was published on 08 December 2021

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Abstract

Ciliary neurotrophic factor (CNTF), which is a neural peptide, has been reported to confer cardioprotective effects. However, whether CNTF-based gene delivery could prevent cardiac remodeling in diabetes mellitus remains unknown. In this study, we used adeno-associated viral vector serotype 9 (AAV9)-based cardiac gene delivery to test the effects of CNTF overexpression on adverse ventricular remodeling in streptozotocin-induced type 1 diabetic mice models. Postnatal (P3-P10) mice were peritoneally injected with AAV9 recombinant virus carrying the CNTF gene or EGFP gene. Then, type 1 diabetic models were established by peritoneal injection of streptozotocin (200 mg/kg) in 7-week-old female mice injected with AAV9. 4 weeks later after the establishment of type 1 diabetes mellitus, mouse hearts were removed to assess the degree of cardiac remodeling. We found that CNTF overexpression in mouse cardiomyocytes exacerbated cell apoptosis and cardiac fibrosis coupled with an increased inflammatory response in the heart tissue of diabetic female mice. Taken together, our results suggested that cardiac CNTF gene delivery may not be beneficial in alleviating adverse cardiac remodeling in type 1 diabetes female mice.

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Data Availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. All data generated or analyzed during this study are included in this published article.

Code Availability

No code was generated or used during the study.

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Funding

This work was supported by financial support from Wuhan University (Grant number: 2042019kf0074) and jointly supported by the National Natural Science Foundation of China (No. 81401304), the Natural Science Foundation of Hubei Province, China (No. 2019CFB621), the Health Commission of Hubei Province and Wuhan University of Science and Technology Joint Foundation (WJ2019H219).

Author information

Author notes

  1. Peng Zhong and Jianye Peng contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Peng Zhong & Tao Liu

  2. Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China

    Peng Zhong & Tao Liu

  3. Hubei Key Laboratory of Cardiology, Wuhan, 430060, China

    Peng Zhong & Tao Liu

  4. The Second Affiliated Hospital, Department of Cardiovascular Medicine, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China

    Jianye Peng

  5. The Second Affiliated Hospital, Key Laboratory of Heart Failure Prevention & Treatment of Hengyang, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China

    Jianye Peng

  6. Department of Emergency, Shenzhen Hospital, Southern Medical University, Shenzhen, 518101, People’s Republic of China

    Hua-sheng Ding

  7. Department of Emergency, Puren Hospital, Wuhan University of Science and Technology, Wuhan, 430081, People’s Republic of China

    Hua-sheng Ding

  8. Department of Cardiology Research Institute, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei, China

    Peng Zhong

Authors
  1. Peng Zhong
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  2. Jianye Peng
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  3. Tao Liu
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  4. Hua-sheng Ding
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Contributions

PZ and HSD conceptualized the study and designed the experiments. PZ, JYP, and TL perfumed experiments and researched and analyzed data. PZ wrote the manuscript with all co-authors revising it critically for important intellectual content. All authors approved the final version of the manuscript.

Corresponding authors

Correspondence to Peng Zhong or Hua-sheng Ding.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical Approval

The animal experiments were approved by the ethics committee of Wuhan University. This study conforms to the NIH Guide for the Care and Use of Laboratory Animals (NIH publication No.85-23, revised 1996).

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Communicated by Martin Štěrba.

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The original online version of this article was revised: “Hua-sheng Ding is the co-corresponding author of the article”.

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Zhong, P., Peng, J., Liu, T. et al. AAV9-Mediated Cardiac CNTF Overexpression Exacerbated Adverse Cardiac Remodeling in Streptozotocin-Induced Type 1 Diabetic Models. Cardiovasc Toxicol 22, 88–96 (2022). https://doi.org/10.1007/s12012-021-09706-6

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  • DOI: https://doi.org/10.1007/s12012-021-09706-6

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