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

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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.

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Abbreviations

β-MHC:

Myosin heavy chain beta

ANP:

Atrial natriuretic peptide

BNP:

Brain natriuretic peptide

CSA:

Cross-sectional area

CVF:

Collagen volume fraction

DPHP:

Dex-PCL-HEMA/ PNIPAAm

ECM:

Extracellular matrix

LAD:

Left coronary artery

LV:

Left ventricle

LVEDD:

LV end-diastolic diameter

LVESD:

LV end-systolic diameter

LVFS:

Left ventricular fractional shortening

HF:

Heart failure

MI:

Myocardial infarction

NIZ:

Non-infarct zone

PEG:

Polyethylene glycol

TGF-β1:

Transforming growth factor beta1

References

  1. 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.

    Article  Google Scholar 

  2. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 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.

    Article  PubMed  Google Scholar 

  5. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. 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.

    Article  PubMed  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  9. 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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We gratefully acknowledge Dr. Hong-gang Chu for technical support with echocardiography.

Funding

This study was supported by grants from the National Key Basic Research Program of China (2011CB606202), the National Nature Science Foundation of China (81170307), and the Fundamental Research Funds for the Central Universities (2042014kf0158).

Author information

Author notes

  1. Pan-pan Chen

    Present address: People’s Hospital of Fangcheng County, Nanyang, Henan, China

Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, People’s Republic of China

    Ying Wen, Xiao-yan Li, Meng-long Wang, Pan-pan Chen, Yang Liu & Xue-jun Jiang

  2. Cardiovascular Research Institute, Wuhan University, Wuhan, People’s Republic of China

    Ying Wen, Xiao-yan Li, Meng-long Wang, Pan-pan Chen, Yang Liu & Xue-jun Jiang

  3. Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China

    Ying Wen

  4. Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, Hubei, People’s Republic of China

    Ze-yong Li & Xian-zheng Zhang

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Correspondence to Xue-jun Jiang.

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Research Involving Human Participants

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Animal Research Ethical Approval

The study protocols were approved by the Institutional Animal Care Committee from Wuhan University, People’s Republic of China. NIH guidelines (NIH publication no. 85-23, revised 1996) were followed during the investigation for experimental animal use.

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Wen, Y., Li, Xy., Li, Zy. et al. Intra-myocardial Delivery of a Novel Thermosensitive Hydrogel Inhibits Post-infarct Heart Failure After Degradation in Rat. J. of Cardiovasc. Trans. Res. 13, 677–685 (2020). https://doi.org/10.1007/s12265-019-09941-x

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