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A collagen hydrogel loaded with HDAC7-derived peptide promotes the regeneration of infarcted myocardium with functional improvement in a rodent model

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A collagen hydrogel loaded with HDAC7-derived peptide promotes the regeneration of infarcted myocardium with functional improvement in a rodent model. / Zhang, Yue; Zhu, Dashuai; Wei, Yongzhen; Wu, Yifan; Cui, Weilong; Liuqin, Lingfei; Fan, Guanwei; Yang, Qiang; Wang, Zhexiang; Xu, Zhelong; Kong, Deling; Zeng, Lingfang; Zhao, Qiang.

In: Acta Biomaterialia, Vol. 86, 01.03.2019, p. 223-234.

Research output: Contribution to journalArticle

Harvard

Zhang, Y, Zhu, D, Wei, Y, Wu, Y, Cui, W, Liuqin, L, Fan, G, Yang, Q, Wang, Z, Xu, Z, Kong, D, Zeng, L & Zhao, Q 2019, 'A collagen hydrogel loaded with HDAC7-derived peptide promotes the regeneration of infarcted myocardium with functional improvement in a rodent model', Acta Biomaterialia, vol. 86, pp. 223-234. https://doi.org/10.1016/j.actbio.2019.01.022

APA

Zhang, Y., Zhu, D., Wei, Y., Wu, Y., Cui, W., Liuqin, L., ... Zhao, Q. (2019). A collagen hydrogel loaded with HDAC7-derived peptide promotes the regeneration of infarcted myocardium with functional improvement in a rodent model. Acta Biomaterialia, 86, 223-234. https://doi.org/10.1016/j.actbio.2019.01.022

Vancouver

Zhang Y, Zhu D, Wei Y, Wu Y, Cui W, Liuqin L et al. A collagen hydrogel loaded with HDAC7-derived peptide promotes the regeneration of infarcted myocardium with functional improvement in a rodent model. Acta Biomaterialia. 2019 Mar 1;86:223-234. https://doi.org/10.1016/j.actbio.2019.01.022

Author

Zhang, Yue ; Zhu, Dashuai ; Wei, Yongzhen ; Wu, Yifan ; Cui, Weilong ; Liuqin, Lingfei ; Fan, Guanwei ; Yang, Qiang ; Wang, Zhexiang ; Xu, Zhelong ; Kong, Deling ; Zeng, Lingfang ; Zhao, Qiang. / A collagen hydrogel loaded with HDAC7-derived peptide promotes the regeneration of infarcted myocardium with functional improvement in a rodent model. In: Acta Biomaterialia. 2019 ; Vol. 86. pp. 223-234.

Bibtex Download

@article{cc6dad57707c4776a25212ed932697c7,
title = "A collagen hydrogel loaded with HDAC7-derived peptide promotes the regeneration of infarcted myocardium with functional improvement in a rodent model",
abstract = "Myocardial infarction (MI) leads to the loss of cardiomyocytes, left ventricle (LV) dilation, and cardiac dysfunction, eventually developing into heart failure. Most of the strategies for MI therapy require biomaterials that can support tissue regeneration. In this study, we hypothesized that the extracellular matrix (ECM)-derived collagen I hydrogel loaded with histone deacetylase 7 (HDAC7)-derived-phosphorylated 7-amino-acid peptide (7Ap) could restrain LV remodeling and improve cardiac function after MI. An MI model was established by ligation of the left anterior descending coronary artery (LAD) of C57/B6 mice. The 7Ap-loaded collagen I hydrogel was intramyocardially injected to the infarcted region of the LV wall of the heart. After local delivery, the 7Ap-collagen increased neo-microvessel formation, enhanced stem cell antigen-1 positive (Sca-1+) stem cell recruitment and differentiation, decreased cellular apoptosis, and promoted cardiomyocyte cycle progression. Furthermore, the 7Ap-collagen restricted the fibrosis of the LV wall, reduced the infarct wall thinning, and improved cardiac performance significantly at 2 weeks post-MI. These results highlight the promising implication of 7Ap-collagen as a novel candidate for MI therapy.Statement of SignificanceThe mammalian myocardium has a limited regenerative capability following myocardial infarction (MI). MI leads to extensive loss of cardiomyocytes, thus culminating in adverse cardiac remodeling and congestive heart failure. In situ tissue regeneration through endogenous cell mobilization has great potential for tissue regeneration. A 7-amino-acid-peptide (7A) domain encoded by a short open-reading frame (sORF) of the HDAC7 gene. The phosphorylated from of 7A (7Ap) has been reported to promote in situ tissue repair via the mobilization and recruitment of endogenous stem cell antigen-1 positive (Sca-l+) stem cells. In this study, 7Ap was shown to improve H9C2 cell survival, in vitro. In vivo investigations in a mouse MI model demonstrated that intra-myocardial delivery of 7Ap-loaded collagen hydrogel promoted neovascularization, stimulated Sca-l+ stem cell recruitment and differentiation, reduced cardiomyocyte apoptosis and promoted cell cycle progression. As a result, treated infarcted hearts had increased wall thickness, had improved heart function and exhibited attenuation of adverse cardiac remodeling, observed for up to 2 weeks. Overall, these results highlighted the positive impact of implanting 7Ap-collagen as a novel constituent for MI repair.",
keywords = "7Ap peptide, Angiogenesis, Anti-apoptosis, Cardiac functional recovery, Collagen I hydrogel, Myocardial infarction, Stem cell recruitment",
author = "Yue Zhang and Dashuai Zhu and Yongzhen Wei and Yifan Wu and Weilong Cui and Lingfei Liuqin and Guanwei Fan and Qiang Yang and Zhexiang Wang and Zhelong Xu and Deling Kong and Lingfang Zeng and Qiang Zhao",
year = "2019",
month = "3",
day = "1",
doi = "10.1016/j.actbio.2019.01.022",
language = "English",
volume = "86",
pages = "223--234",
journal = "Acta Biomaterialia",
issn = "1742-7061",
publisher = "Elsevier BV",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - A collagen hydrogel loaded with HDAC7-derived peptide promotes the regeneration of infarcted myocardium with functional improvement in a rodent model

AU - Zhang, Yue

AU - Zhu, Dashuai

AU - Wei, Yongzhen

AU - Wu, Yifan

AU - Cui, Weilong

AU - Liuqin, Lingfei

AU - Fan, Guanwei

AU - Yang, Qiang

AU - Wang, Zhexiang

AU - Xu, Zhelong

AU - Kong, Deling

AU - Zeng, Lingfang

AU - Zhao, Qiang

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Myocardial infarction (MI) leads to the loss of cardiomyocytes, left ventricle (LV) dilation, and cardiac dysfunction, eventually developing into heart failure. Most of the strategies for MI therapy require biomaterials that can support tissue regeneration. In this study, we hypothesized that the extracellular matrix (ECM)-derived collagen I hydrogel loaded with histone deacetylase 7 (HDAC7)-derived-phosphorylated 7-amino-acid peptide (7Ap) could restrain LV remodeling and improve cardiac function after MI. An MI model was established by ligation of the left anterior descending coronary artery (LAD) of C57/B6 mice. The 7Ap-loaded collagen I hydrogel was intramyocardially injected to the infarcted region of the LV wall of the heart. After local delivery, the 7Ap-collagen increased neo-microvessel formation, enhanced stem cell antigen-1 positive (Sca-1+) stem cell recruitment and differentiation, decreased cellular apoptosis, and promoted cardiomyocyte cycle progression. Furthermore, the 7Ap-collagen restricted the fibrosis of the LV wall, reduced the infarct wall thinning, and improved cardiac performance significantly at 2 weeks post-MI. These results highlight the promising implication of 7Ap-collagen as a novel candidate for MI therapy.Statement of SignificanceThe mammalian myocardium has a limited regenerative capability following myocardial infarction (MI). MI leads to extensive loss of cardiomyocytes, thus culminating in adverse cardiac remodeling and congestive heart failure. In situ tissue regeneration through endogenous cell mobilization has great potential for tissue regeneration. A 7-amino-acid-peptide (7A) domain encoded by a short open-reading frame (sORF) of the HDAC7 gene. The phosphorylated from of 7A (7Ap) has been reported to promote in situ tissue repair via the mobilization and recruitment of endogenous stem cell antigen-1 positive (Sca-l+) stem cells. In this study, 7Ap was shown to improve H9C2 cell survival, in vitro. In vivo investigations in a mouse MI model demonstrated that intra-myocardial delivery of 7Ap-loaded collagen hydrogel promoted neovascularization, stimulated Sca-l+ stem cell recruitment and differentiation, reduced cardiomyocyte apoptosis and promoted cell cycle progression. As a result, treated infarcted hearts had increased wall thickness, had improved heart function and exhibited attenuation of adverse cardiac remodeling, observed for up to 2 weeks. Overall, these results highlighted the positive impact of implanting 7Ap-collagen as a novel constituent for MI repair.

AB - Myocardial infarction (MI) leads to the loss of cardiomyocytes, left ventricle (LV) dilation, and cardiac dysfunction, eventually developing into heart failure. Most of the strategies for MI therapy require biomaterials that can support tissue regeneration. In this study, we hypothesized that the extracellular matrix (ECM)-derived collagen I hydrogel loaded with histone deacetylase 7 (HDAC7)-derived-phosphorylated 7-amino-acid peptide (7Ap) could restrain LV remodeling and improve cardiac function after MI. An MI model was established by ligation of the left anterior descending coronary artery (LAD) of C57/B6 mice. The 7Ap-loaded collagen I hydrogel was intramyocardially injected to the infarcted region of the LV wall of the heart. After local delivery, the 7Ap-collagen increased neo-microvessel formation, enhanced stem cell antigen-1 positive (Sca-1+) stem cell recruitment and differentiation, decreased cellular apoptosis, and promoted cardiomyocyte cycle progression. Furthermore, the 7Ap-collagen restricted the fibrosis of the LV wall, reduced the infarct wall thinning, and improved cardiac performance significantly at 2 weeks post-MI. These results highlight the promising implication of 7Ap-collagen as a novel candidate for MI therapy.Statement of SignificanceThe mammalian myocardium has a limited regenerative capability following myocardial infarction (MI). MI leads to extensive loss of cardiomyocytes, thus culminating in adverse cardiac remodeling and congestive heart failure. In situ tissue regeneration through endogenous cell mobilization has great potential for tissue regeneration. A 7-amino-acid-peptide (7A) domain encoded by a short open-reading frame (sORF) of the HDAC7 gene. The phosphorylated from of 7A (7Ap) has been reported to promote in situ tissue repair via the mobilization and recruitment of endogenous stem cell antigen-1 positive (Sca-l+) stem cells. In this study, 7Ap was shown to improve H9C2 cell survival, in vitro. In vivo investigations in a mouse MI model demonstrated that intra-myocardial delivery of 7Ap-loaded collagen hydrogel promoted neovascularization, stimulated Sca-l+ stem cell recruitment and differentiation, reduced cardiomyocyte apoptosis and promoted cell cycle progression. As a result, treated infarcted hearts had increased wall thickness, had improved heart function and exhibited attenuation of adverse cardiac remodeling, observed for up to 2 weeks. Overall, these results highlighted the positive impact of implanting 7Ap-collagen as a novel constituent for MI repair.

KW - 7Ap peptide

KW - Angiogenesis

KW - Anti-apoptosis

KW - Cardiac functional recovery

KW - Collagen I hydrogel

KW - Myocardial infarction

KW - Stem cell recruitment

UR - http://www.scopus.com/inward/record.url?scp=85060326213&partnerID=8YFLogxK

U2 - 10.1016/j.actbio.2019.01.022

DO - 10.1016/j.actbio.2019.01.022

M3 - Article

VL - 86

SP - 223

EP - 234

JO - Acta Biomaterialia

JF - Acta Biomaterialia

SN - 1742-7061

ER -

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