4.7 Article

V1-Cal hydrogelation enhances its effects on ventricular remodeling reduction and cardiac function improvement post myocardial infarction

Journal

CHEMICAL ENGINEERING JOURNAL
Volume 433, Issue -, Pages -

Publisher

ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2021.134450

Keywords

Myocardial infarction; Supramolecular hydrogel; Sustained release; TRPV1; V1-Cal

Funding

  1. National Natural Science Foundation of China [21725505, 81970231]
  2. Open Research Fund of State Key Laboratory of Bioelectronics of Southeast University [Sklb2021p09]
  3. National Institutes of Health NIGMS [GM119522]

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In this study, a new supramolecular hydrogel V1-Cal/NapFFY was developed, which significantly enhanced the therapeutic effects of V1-Cal on myocardial infarction and improved cardiac function. The hydrogel demonstrated sustained release of V1-Cal for more than two weeks and effectively reduced TRPV1 expression, apoptosis, and inflammatory factors in vivo experiments.
Myocardial infarction (MI) is a major cause of disability and mortality worldwide. A cell permeable peptide V1 Cal has shown remarkable therapeutic effects on MI. However, using V1-Cal to improve long-term cardiac function after MI is presently limited by its short half-life. Herein, we co-assembled V1-Cal with a well-known hydrogelator Nap-Phe-Phe-Tyr (NapFFY) to obtain a new supramolecular hydrogel V1-Cal/NapFFY. We found that the hydrogel could significantly enhance the therapeutic effects of V1-Cal on ventricular remodeling reduction and cardiac function improvement in a myocardial infarction rat model. In vitro experiments indicated that co-assembly of V1-Cal with NapFFY significantly increased mechanic strength of the hydrogel, enabling a sustained release of V1-Cal for more than two weeks. In vivo experiments supported that sustained release of V1 Cal from V1-Cal/NapFFY hydrogel could effectively decrease the expression and activation of TRPV1, reduce apoptosis and the release of inflammatory factors in a MI rat model. In particular, V1-Cal/NapFFY hydrogel significantly decreased infarct size and fibrosis, while improved cardiac function 28 days post MI. We anticipate that V1-Cal/NapFFY hydrogel could be used clinically to treat MI in the near future.

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