Volume 113, Issue 5 e37924
RESEARCH ARTICLE

Vascular Endothelial Growth Factor-Mimetic Peptide and Mitochondria-Targeted Antioxidant-Loaded Hydrogel System Improves Repair of Myocardial Infarction in Mice

Qingling Xu

Qingling Xu

School of Basic Medicine, Qingdao University, Qingdao, Shandong, China

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Xinhui Chen

Xinhui Chen

School of Basic Medicine, Qingdao University, Qingdao, Shandong, China

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Shuwei Sun

Shuwei Sun

School of Basic Medicine, Qingdao University, Qingdao, Shandong, China

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Chunyige Zhao

Chunyige Zhao

School of Basic Medicine, Qingdao University, Qingdao, Shandong, China

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Linxin Shi

Linxin Shi

School of Basic Medicine, Qingdao University, Qingdao, Shandong, China

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Han Cheng

Han Cheng

School of Basic Medicine, Qingdao University, Qingdao, Shandong, China

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Ying Liu

Corresponding Author

Ying Liu

Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao, Shandong, China

Correspondence:

Ying Liu ([email protected])

Chunying Shi ([email protected])

Xiang Ao ([email protected])

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Chunying Shi

Corresponding Author

Chunying Shi

School of Basic Medicine, Qingdao University, Qingdao, Shandong, China

Correspondence:

Ying Liu ([email protected])

Chunying Shi ([email protected])

Xiang Ao ([email protected])

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Xiang Ao

Corresponding Author

Xiang Ao

School of Basic Medicine, Qingdao University, Qingdao, Shandong, China

Correspondence:

Ying Liu ([email protected])

Chunying Shi ([email protected])

Xiang Ao ([email protected])

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First published: 07 May 2025
Citations: 1

Funding: This work was supported by Natural Science Foundation of Shandong Province (ZR2023MC168 and ZR2023MH299).

Qingling Xu, Xinhui Chen and Shuwei Sun have contributed equally to this work and share first authorship.

ABSTRACT

Myocardial infarction (MI) is a pathological state characterized by persistent ischemia of the heart. Following MI, the structural and functional remodeling of the myocardium and vasculature involves oxidative stress and mitochondrial dysfunction, which exacerbate myocardial injury. Currently, there are limited effective treatments available to alleviate MI-induced damage. Vascular endothelial growth factor-mimetic (QK) peptides and mitochondria-targeted Szeto–Schiller (SS31) peptides have been extensively investigated for their therapeutic potential in various ischemic cardiomyopathies. However, traditional topical agents used in myocardial ischemia treatment suffer from limitations such as transient retention or undesirable diffusion of the drug. Consequently, a controlled drug delivery system capable of delivering QK and SS31 has gained significant attention for repair. In this study, we constructed self-assembled nanofibrous hydrogels incorporating QK and SS31 with customizable peptide amphiphilic (PA) molecules, resulting in PA1-QK and PA2-SS31 formulations. In vitro experiments demonstrated that both QK and SS31 effectively inhibited mitochondrial damage and apoptosis in a cellular hypoxia/reoxygenation (H/R) model. In vivo studies using a mouse MI model revealed that PA1-QK and PA2-SS31 significantly promoted vascular regeneration, attenuated mitochondrial dysfunction and apoptosis, and facilitated the recovery of cardiac structure and function. These results suggest that PA1-QK and PA2-SS31-loaded self-assembled nanofiber hydrogels represent an effective drug delivery system for promoting regenerative repair of myocardium and blood vessels following MI.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

All data required of the paper are included in the paper and/or the Supplementary For Peer Review Materials. The other related data may be requested from the authors.

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