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Journal of Cardiovascular Translational Research

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01-10-2020 | Myocardial Infarction | Original Article

Intra-myocardial Delivery of a Novel Thermosensitive Hydrogel Inhibits Post-infarct Heart Failure After Degradation in Rat

Authors: Ying Wen, Xiao-yan Li, Ze-yong Li, Meng-long Wang, Pan-pan Chen, Yang Liu, Xian-zheng Zhang, Xue-jun Jiang

Published in: Journal of Cardiovascular Translational Research | Issue 5/2020

Abstract

Whether intra-myocardial delivery of hydrogel can prevent post-infarct heart failure (HF) in a long follow-up period, especially after it is degraded, remains unclear. In this study, Dex-PCL-HEMA/PNIPAAm (DPHP) hydrogel was delivered into peri-infarct myocardium of rat when coronary artery was ligated, while PBS was employed as control. Twelve weeks later, compared with control, left ventricle remodeling was attenuated and cardiac function was preserved; serum brain natriuretic peptide, cardiac aldosterone, and pulmonary congestion were suppressed in hydrogel group. Pro-fibrogenic mRNA increased in infarct area while decreased in remote zone, as well as hypertrophic mRNA. These data proves DPHP hydrogel suppresses ventricular remodeling and HF by promoting fibrotic healing in infarct area and inhibiting reactive fibrosis and hypertrophy in remote zone. Timely intra-myocardial hydrogel implantation is an effective strategy to inhibit post-infarct cardiac remodeling and have a long-term beneficial effect even after it has been biodegraded.

Benjamin, E. J., Muntner, P., Alonso, A., Bittencourt, M. S., Callaway, C. W., Carson, A. P., et al. (2019). Heart Disease and Stroke statistics-2019 update: a report from the American Heart Association. Circulation, 139(10), e56–e528. https://doi.org/10.1161/CIR.0000000000000659.CrossRef

Pena, B., Laughter, M., Jett, S., Rowland, T. J., Taylor, M. R. G., Mestroni, L., et al. (2018). Injectable hydrogels for cardiac tissue engineering. Macromolecular Bioscience, 18(6), e1800079. https://doi.org/10.1002/mabi.201800079.CrossRefPubMedPubMedCentral

Zhou, J., Yang, X., Liu, W., Wang, C., Shen, Y., Zhang, F., et al. (2018). Injectable OPF/graphene oxide hydrogels provide mechanical support and enhance cell electrical signaling after implantation into myocardial infarct. Theranostics, 8(12), 3317–3330. https://doi.org/10.7150/thno.25504.CrossRefPubMedPubMedCentral

Wang, H., Rodell, C. B., Zhang, X., Dusaj, N. N., Gorman 3rd, J. H., Pilla, J. J., et al. (2018). Effects of hydrogel injection on borderzone contractility post-myocardial infarction. Biomechanics and Modeling in Mechanobiology, 17(5), 1533–1542. https://doi.org/10.1007/s10237-018-1039-2.CrossRefPubMed

Choy, J. S., Leng, S., Acevedo-Bolton, G., Shaul, S., Fu, L., Guo, X., et al. (2018). Efficacy of intramyocardial injection of Algisyl-LVR for the treatment of ischemic heart failure in swine. International Journal of Cardiology, 255, 129–135. https://doi.org/10.1016/j.ijcard.2017.09.179.CrossRefPubMedPubMedCentral

Mann, D. L., Lee, R. J., Coats, A. J., Neagoe, G., Dragomir, D., Pusineri, E., et al. (2016). One-year follow-up results from AUGMENT-HF: a multicentre randomized controlled clinical trial of the efficacy of left ventricular augmentation with Algisyl in the treatment of heart failure. European Journal of Heart Failure, 18(3), 314–325. https://doi.org/10.1002/ejhf.449.CrossRefPubMed

Rao, S. V., Zeymer, U., Douglas, P. S., Al-Khalidi, H., White, J. A., Liu, J., et al. (2016). Bioabsorbable intracoronary matrix for prevention of ventricular remodeling after myocardial infarction. Journal of the American College of Cardiology, 68(7), 715–723. https://doi.org/10.1016/j.jacc.2016.05.053.CrossRefPubMed

Frey, N., Linke, A., Suselbeck, T., Muller-Ehmsen, J., Vermeersch, P., Schoors, D., et al. (2014). Intracoronary delivery of injectable bioabsorbable scaffold (IK-5001) to treat left ventricular remodeling after ST-elevation myocardial infarction: a first-in-man study. Circulation. Cardiovascular Interventions, 7(6), 806–812. https://doi.org/10.1161/CIRCINTERVENTIONS.114.001478.CrossRefPubMed

Leor, J., Tuvia, S., Guetta, V., Manczur, F., Castel, D., Willenz, U., et al. (2009). Intracoronary injection of in situ forming alginate hydrogel reverses left ventricular remodeling after myocardial infarction in swine. Journal of the American College of Cardiology, 54(11), 1014–1023. https://doi.org/10.1016/j.jacc.2009.06.010.CrossRefPubMed

10.

Wu, D. Q., Qiu, F., Wang, T., Jiang, X. J., Zhang, X. Z., & Zhuo, R. X. (2009). Toward the development of partially biodegradable and injectable thermoresponsive hydrogels for potential biomedical applications. ACS Applied Materials & Interfaces, 1(2), 319–327. https://doi.org/10.1021/am8000456.CrossRef

11.

Xiao-Yan, L. T., Wang ; Xue-Jun, Jiang ; Tao, Lin ; Shan, Ren (2009). 3-Dimension (3-D) culture of endothelial cells in vitro Tao. Paper presented at the 2009 3rd International Conference on Bioinformatics and Biomedical Engineering, Beijing, China, 11–13 June 2009.

12.

Wang, T., Wu, D. Q., Jiang, X. J., Zhang, X. Z., Li, X. Y., Zhang, J. F., et al. (2009). Novel thermosensitive hydrogel injection inhibits post-infarct ventricle remodelling. European Journal of Heart Failure, 11(1), 14–19. https://doi.org/10.1093/eurjhf/hfn009.CrossRefPubMed

13.

Li, X. Y., Wang, T., Jiang, X. J., Lin, T., Wu, D. Q., Zhang, X. Z., et al. (2010). Injectable hydrogel helps bone marrow-derived mononuclear cells restore infarcted myocardium. Cardiology, 115(3), 194–199. https://doi.org/10.1159/000281840.CrossRefPubMed

14.

He, Y. Y., Wen, Y., Zheng, X. X., & Jiang, X. J. (2013). Intramyocardial delivery of HMGB1 by a novel thermosensitive hydrogel attenuates cardiac remodeling and improves cardiac function after myocardial infarction. Journal of Cardiovascular Pharmacology, 61(4), 283–290. https://doi.org/10.1097/FJC.0b013e31827ecd50.CrossRefPubMed

15.

Zhu, H., Jiang, X., Li, X., Hu, M., Wan, W., Wen, Y., et al. (2016). Intramyocardial delivery of VEGF165 via a novel biodegradable hydrogel induces angiogenesis and improves cardiac function after rat myocardial infarction. Heart and Vessels, 31(6), 963–975. https://doi.org/10.1007/s00380-015-0710-0.CrossRefPubMed

16.

Wan, W. G., Jiang, X. J., Li, X. Y., Zhang, C., Yi, X., Ren, S., et al. (2014). Enhanced cardioprotective effects mediated by plasmid containing the short-hairpin RNA of angiotensin converting enzyme with a biodegradable hydrogel after myocardial infarction. Journal of Biomedical Materials Research. Part A, 102(10), 3452–3458. https://doi.org/10.1002/jbm.a.35014.CrossRefPubMed

17.

Landa, N., Miller, L., Feinberg, M. S., Holbova, R., Shachar, M., Freeman, I., et al. (2008). Effect of injectable alginate implant on cardiac remodeling and function after recent and old infarcts in rat. Circulation, 117(11), 1388–1396. https://doi.org/10.1161/CIRCULATIONAHA.107.727420.CrossRefPubMed

18.

Burchfield, J. S., Xie, M., & Hill, J. A. (2013). Pathological ventricular remodeling: mechanisms: part 1 of 2. Circulation, 128(4), 388–400. https://doi.org/10.1161/CIRCULATIONAHA.113.001878.CrossRefPubMedPubMedCentral

19.

Gajarsa, J. J., & Kloner, R. A. (2011). Left ventricular remodeling in the post-infarction heart: a review of cellular, molecular mechanisms, and therapeutic modalities. Heart Failure Reviews, 16(1), 13–21. https://doi.org/10.1007/s10741-010-9181-7.CrossRefPubMed

20.

Wu, Q. Q., Xiao, Y., Yuan, Y., Ma, Z. G., Liao, H. H., Liu, C., et al. (2017). Mechanisms contributing to cardiac remodelling. Clinical Science (London, England), 131(18), 2319–2345. https://doi.org/10.1042/CS20171167.CrossRef

21.

Zhu, Y., Matsumura, Y., & Wagner, W. R. (2017). Ventricular wall biomaterial injection therapy after myocardial infarction: advances in material design, mechanistic insight and early clinical experiences. Biomaterials, 129, 37–53. https://doi.org/10.1016/j.biomaterials.2017.02.032.CrossRefPubMedPubMedCentral

22.

Frangogiannis, N. G. (2019). Cardiac fibrosis: cell biological mechanisms, molecular pathways and therapeutic opportunities. Molecular Aspects of Medicine, 65, 70–99. https://doi.org/10.1016/j.mam.2018.07.001.CrossRefPubMed

23.

van den Borne, S. W., Diez, J., Blankesteijn, W. M., Verjans, J., Hofstra, L., & Narula, J. (2010). Myocardial remodeling after infarction: the role of myofibroblasts. Nature Reviews. Cardiology, 7(1), 30–37. https://doi.org/10.1038/nrcardio.2009.199.CrossRefPubMed

24.

Fraccarollo, D., Galuppo, P., & Bauersachs, J. (2012). Novel therapeutic approaches to post-infarction remodelling. Cardiovascular Research, 94(2), 293–303. https://doi.org/10.1093/cvr/cvs109.CrossRefPubMed

25.

Halmosi, R., Deres, L., Gal, R., Eros, K., Sumegi, B., & Toth, K. (2016). PARP inhibition and postinfarction myocardial remodeling. International Journal of Cardiology, 217(Suppl), S52–S59. https://doi.org/10.1016/j.ijcard.2016.06.223.CrossRefPubMed

26.

Gaffey, A. C., Chen, M. H., Trubelja, A., Venkataraman, C. M., Chen, C. W., Chung, J. J., et al. (2018). Delivery of progenitor cells with injectable shear-thinning hydrogel maintains geometry and normalizes strain to stabilize cardiac function after ischemia. The Journal of Thoracic and Cardiovascular Surgery. https://doi.org/10.1016/j.jtcvs.2018.07.117.

27.

Dobner, S., Bezuidenhout, D., Govender, P., Zilla, P., & Davies, N. (2009). A synthetic non-degradable polyethylene glycol hydrogel retards adverse post-infarct left ventricular remodeling. Journal of Cardiac Failure, 15(7), 629–636. https://doi.org/10.1016/j.cardfail.2009.03.003.CrossRefPubMed

28.

Wassenaar, J. W., Gaetani, R., Garcia, J. J., Braden, R. L., Luo, C. G., Huang, D., et al. (2016). Evidence for mechanisms underlying the functional benefits of a myocardial matrix hydrogel for post-MI treatment. Journal of the American College of Cardiology, 67(9), 1074–1086. https://doi.org/10.1016/j.jacc.2015.12.035.CrossRefPubMedPubMedCentral

29.

Wang, R. M., & Christman, K. L. (2016). Decellularized myocardial matrix hydrogels: in basic research and preclinical studies. Advanced Drug Delivery Reviews, 96, 77–82. https://doi.org/10.1016/j.addr.2015.06.002.CrossRefPubMed

Title: Intra-myocardial Delivery of a Novel Thermosensitive Hydrogel Inhibits Post-infarct Heart Failure After Degradation in Rat
Authors: Ying Wen
Xiao-yan Li
Ze-yong Li
Meng-long Wang
Pan-pan Chen
Yang Liu
Xian-zheng Zhang
Xue-jun Jiang
Publication date: 01-10-2020
Publisher: Springer US
Keywords: Myocardial Infarction
Heart Failure
Published in: Journal of Cardiovascular Translational Research / Issue 5/2020
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI: https://doi.org/10.1007/s12265-019-09941-x

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