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V1-Cal水凝胶化增强了其对心肌梗死后减少心室重构和改善心脏功能的作用。

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

作者信息

Wang Bin, Wu Chengfan, He Shufang, Wang Yaguang, Wang Di, Tao Hui, Wang Chenchen, Pang Xiaoxi, Li Fei, Yuan Yue, Gross Eric R, Liang Gaolin, Zhang Ye

机构信息

Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei 230601, PR China.

Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, 678 Furong Road, Hefei 230601, PR China.

出版信息

Chem Eng J. 2022 Apr 1;433(Pt 1). doi: 10.1016/j.cej.2021.134450. Epub 2022 Jan 4.

Abstract

Myocardial infarction (MI) is a major cause of disability and mortality worldwide. A cell permeable peptide V1-Cal has shown remarkable therapeutic effects on ML 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. 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. 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.

摘要

心肌梗死(MI)是全球致残和致死的主要原因。一种可穿透细胞的肽V1-Cal已显示出对心肌梗死具有显著治疗效果。然而,目前使用V1-Cal改善心肌梗死后的长期心脏功能受到其半衰期短的限制。在此,我们将V1-Cal与一种知名的水凝胶剂Nap-Phe-Phe-Tyr(NapFFY)共组装,以获得一种新的超分子水凝胶V1-Cal/NapFFY。我们发现,在心肌梗死大鼠模型中,该水凝胶可显著增强V1-Cal对减少心室重塑和改善心脏功能的治疗效果。实验表明,V1-Cal与NapFFY的共组装显著提高了水凝胶的机械强度,使V1-Cal能够持续释放两周以上。实验支持,V1-Cal从V1-Cal/NapFFY水凝胶中的持续释放可有效降低TRPV1的表达和激活,减少心肌梗死大鼠模型中的细胞凋亡和炎症因子释放。特别是,V1-Cal/NapFFY水凝胶在心肌梗死后28天显著减小梗死面积和纤维化,同时改善心脏功能。我们预计,在不久的将来,V1-Cal/NapFFY水凝胶可用于临床治疗心肌梗死。

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