Evaluation of cardiac regeneration through electrocardiograms in Danio rerio in state of hypobaric hypoxia
Cardiovascular diseases remain a leading cause of mortality globally. Heart failure often results in irreversible damage and the formation of non-contractile fibrotic scars that are not capable of proper electrical transmission as they are not an adequate substitute for cardiomyocytes. The scars are...
- Autores:
-
Arenas Pérez, Camilo
- Tipo de recurso:
- Trabajo de grado de pregrado
- Fecha de publicación:
- 2025
- Institución:
- Universidad de los Andes
- Repositorio:
- Séneca: repositorio Uniandes
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.uniandes.edu.co:1992/75796
- Acceso en línea:
- https://hdl.handle.net/1992/75796
- Palabra clave:
- Heart Regeneration
Electrocardiogram
Hypoxia
Normoxia
Danio rerio
Hypobaric hypoxia
Biología
- Rights
- openAccess
- License
- Attribution 4.0 International
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Evaluation of cardiac regeneration through electrocardiograms in Danio rerio in state of hypobaric hypoxia |
| title |
Evaluation of cardiac regeneration through electrocardiograms in Danio rerio in state of hypobaric hypoxia |
| spellingShingle |
Evaluation of cardiac regeneration through electrocardiograms in Danio rerio in state of hypobaric hypoxia Heart Regeneration Electrocardiogram Hypoxia Normoxia Danio rerio Hypobaric hypoxia Biología |
| title_short |
Evaluation of cardiac regeneration through electrocardiograms in Danio rerio in state of hypobaric hypoxia |
| title_full |
Evaluation of cardiac regeneration through electrocardiograms in Danio rerio in state of hypobaric hypoxia |
| title_fullStr |
Evaluation of cardiac regeneration through electrocardiograms in Danio rerio in state of hypobaric hypoxia |
| title_full_unstemmed |
Evaluation of cardiac regeneration through electrocardiograms in Danio rerio in state of hypobaric hypoxia |
| title_sort |
Evaluation of cardiac regeneration through electrocardiograms in Danio rerio in state of hypobaric hypoxia |
| dc.creator.fl_str_mv |
Arenas Pérez, Camilo |
| dc.contributor.advisor.none.fl_str_mv |
Garavito Aguilar, Zayra Viviana Vásquez Vélez, Isabel Cristina |
| dc.contributor.author.none.fl_str_mv |
Arenas Pérez, Camilo |
| dc.contributor.researchgroup.none.fl_str_mv |
Facultad de Ciencias::Laboratorio de Biología del desarrollo (Bioldes) |
| dc.subject.keyword.eng.fl_str_mv |
Heart Regeneration Electrocardiogram Hypoxia Normoxia Danio rerio Hypobaric hypoxia |
| topic |
Heart Regeneration Electrocardiogram Hypoxia Normoxia Danio rerio Hypobaric hypoxia Biología |
| dc.subject.themes.spa.fl_str_mv |
Biología |
| description |
Cardiovascular diseases remain a leading cause of mortality globally. Heart failure often results in irreversible damage and the formation of non-contractile fibrotic scars that are not capable of proper electrical transmission as they are not an adequate substitute for cardiomyocytes. The scars are made of a non-contractile collagenous tissue that thins and compacts over time, increasing stress to the heart walls causing problems such as arrhythmias. Current research focuses on regenerative approaches to restore the lost cardiac tissue, using model organisms such as zebrafish (Danio rerio) due to their heart regeneration capacity, and similarities to humans in cell composition and electric activity. This study investigates the effects of hypobaric hypoxia on the regeneration processes as the hypoxia-inducible factors (HIF) have been seen to change cell metabolism, management of oxidative stress, and angiogenesis likely affecting heart electric activity. This was functionally visualized following the ventricular regeneration process after cryoinjury using electrocardiogram (ECG) analysis. Thus, we assess the cardiac electrical activity throughout the regeneration process of the zebrafish comparing a state of normoxia and a state of hypobaric hypoxia. All ECG data were processed through a principal component analysis, which revealed possible differences in cardiac recovery patterns between hypoxic and normoxic groups. Hypoxia-exposed zebrafish demonstrated potentially faster heart rate recovery, shorter RR intervals, likely influenced by chronic hypoxia adaptations such as enhanced HIF-1α expression and increased sympathetic nerve activity. These findings suggest that hypoxia could make the regeneration process more efficient, and prepare the heart for events of heart failure, which correlates with studies of humans permanently residing in high-altitude regions. |
| publishDate |
2025 |
| dc.date.accessioned.none.fl_str_mv |
2025-01-29T20:23:46Z |
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2025-01-29T20:23:46Z |
| dc.date.issued.none.fl_str_mv |
2025-01-29 |
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Trabajo de grado - Pregrado |
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info:eu-repo/semantics/bachelorThesis |
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info:eu-repo/semantics/acceptedVersion |
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eng |
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eng |
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Arel, E., Rolland, L., Thireau, J., Torrente, AG., Bechard, E., Bride, J., Jopling, C., Demion, M., & Guennec, J.-Y. L. (2022, January 1). Characterization of the adult zebrafish electrocardiogram. bioRxiv. https://doi.org/10.1101/2022.02.02.478776 Bo, B., Li, S., Zhou, K., & Wei, J. (2021). The Regulatory Role of Oxygen Metabolism in Exercise-Induced Cardiomyocyte Regeneration. Frontiers in cell and developmental biology, 9, 664527. https://doi.org/10.3389/fcell.2021.664527 Bocchi, E. A., Arias, A., Verdejo, H., Diez, M., Gómez, E., Castro, P., & Interamerican Society of Cardiology (2013). The reality of heart failure in Latin America. Journal of the American College of Cardiology, 62(11), 949–958. https://doi.org/10.1016/j.jacc.2013.06.013 Boron, W. F. & Boulpaep, E. L. Cardiac Electrophysiology and the Electrocardiogram. Medical Physiology (Third Edition, pp. 483–506). Elsevier. Retrieved 2024, from https://www-clinicalkey-com.ezproxy.uniandes.edu.co/#!/content/book/3-s2.0-B9781455743773000215. Burtscher M. (2013). Effects of living at higher altitudes on mortality: a narrative review. Aging and disease, 5(4), 274–280. https://doi.org/10.14336/AD.2014.0500274 Burtscher, J., Citherlet, T., Camacho-Cardenosa, A., Camacho-Cardenosa, M., Raberin, A., Krumm, B., Hohenauer, E., Egg, M., Lichtblau, M., Müller, J., Rybnikova, E. A., Gatterer, H., Debevec, T., Baillieul, S., Manferdelli, G., Behrendt, T., Schega, L., Ehrenreich, H., Millet, G. P., Gassmann, M., … Mallet, R. T. (2024). Mechanisms underlying the health benefits of intermittent hypoxia conditioning. The Journal of physiology, 602(21), 5757–5783. https://doi.org/10.1113/JP285230 Calbet, J. A., Robach, P., & Lundby, C. (2009). The exercising heart at altitude. Cellular and molecular life sciences : CMLS, 66(22), 3601–3613. https://doi.org/10.1007/s00018-009-0148-6 Chablais, F., Veit, J., Rainer, G. et al. The zebrafish heart regenerates after cryoinjury-induced myocardial infarction. BMC Dev Biol 11, 21 (2011). https://doi.org/10.1186/1471-213X-11-21 Dall, C., Khan, M., Chen, C.-A., & Angelos, M. G. (2016). Oxygen cycling to improve survival of stem cells for myocardial repair: A Review. Life Sciences, 153, 124–131. https://doi.org/10.1016/j.lfs.2016.04.011 Dbouk, H. A., Mroue, R. M., El-Sabban, M. E., & Talhouk, R. S. (2009). Connexins: a myriad of functions extending beyond assembly of gap junction channels. Cell communication and signaling : CCS, 7, 4. https://doi.org/10.1186/1478-811X-7-4 Ezzati, M., Murray Horwitz, M. E., Thomas, D. S., Friedman, A. B., Roach, R., Clark, T., Murray, C. J., & Honigman, B. (2012). Altitude, life expectancy and mortality from ischaemic heart disease, stroke, COPD and cancers: national population-based analysis of US counties. Journal of epidemiology and community health, 66(7), e17. https://doi.org/10.1136/jech.2010.112938 Faeh D, Gutzwiller F, Bopp M. Lower mortality from coronary heart disease and stroke at higher altitudes in Switzerland. Circulation. 2009;120(6):495–501. Faulhaber, M., Gatterer, H., Haider, T., Linser, T., Netzer, N., & Burtscher, M. (2015). Heart rate and blood pressure responses during hypoxic cycles of a 3-week intermittent hypoxia breathing program in patients at risk for or with mild COPD. International journal of chronic obstructive pulmonary disease, 10, 339–345. https://doi.org/10.2147/COPD.S75749 Gao, R., & Ren, J. (2021, July 20). Zebrafish models in therapeutic research of cardiac conduction disease. Frontiers. https://doi.org/10.3389/fcell.2021.731402 Garbern, J. C., & Lee, R. T. (2022). Heart regeneration: 20 years of progress and renewed optimism. Developmental cell, 57(4), 424–439. https://doi.org/10.1016/j.devcel.2022.01.012 González-Rosa, J. M., Burns, C. E., & Burns, C. G. (2017). Zebrafish heart regeneration: 15 years of discoveries. Regeneration (Oxford, England), 4(3), 105–123. https://doi.org/10.1002/reg2.83 Hara H, Takeda N, Komuro I. Pathophysiology and therapeutic potential of cardiac fibrosis. Inflamm Regen. 2017;37(1):1–10 Hochachka P. W. (1998). Mechanism and evolution of hypoxia-tolerance in humans. The Journal of experimental biology, 201(Pt 8), 1243–1254. https://doi.org/10.1242/jeb.201.8.1243 Howe, K., Clark, M., Torroja, C. et al. (2013). The zebrafish reference genome sequence and its relationship to the human genome. Nature 496, 498–503. https://doi.org/10.1038/nature12111 Johnson FL. Pathophysiology and Etiology of Heart Failure. Cardiol Clin [Internet]. 2014;32(1):9–19. Available from: http://dx.doi.org/10.1016/j.ccl.2013.09.015 Jopling, C., Suñé, G., Faucherre, A., Fabregat, C., & Izpisua Belmonte, J. C. (2012). Hypoxia induces myocardial regeneration in zebrafish. Circulation, 126(25), 3017–3027. https://doi.org/10.1161/CIRCULATIONAHA.112.107888 Kotini, M., Barriga, E.H., Leslie, J. et al. Gap junction protein Connexin-43 is a direct transcriptional regulator of N-cadherin in vivo. Nat Commun 9, 3846 (2018). https://doi.org/10.1038/s41467-018-06368-x Mandic, M., Joyce, W., & Perry, S. F. (2021). The evolutionary and physiological significance of the HIF pathway in teleost fishes. Journal of Experimental Biology, 224(18). https://doi.org/10.1242/jeb.231936 Nakada, Y., Canseco, D. C., Thet, S., Abdisalaam, S., Asaithamby, A., Santos, C. X., Shah, A. M., Zhang, H., Faber, J. E., Kinter, M. T., Szweda, L. I., Xing, C., Hu, Z., Deberardinis, R. J., Schiattarella, G., Hill, J. A., Oz, O., Lu, Z., Zhang, C. C., … Sadek, H. A. (2016). Hypoxia induces heart regeneration in adult mice. Nature, 541(7636), 222–227. https://doi.org/10.1038/nature20173 Nemtsas, P., Wettwer, E., Christ, T., Weidinger, G., & Ravens, U. (2010). Adult zebrafish heart as a model for human heart? An electrophysiological study. Journal of molecular and cellular cardiology, 48(1), 161–171. https://doi.org/10.1016/j.yjmcc.2009.08.034 Ostadal B, Kolar F. (2007). Cardiac adaptation to chronic high-altitude hypoxia: Beneficial and adverse effects. Respir Physiol Neurobiol. 2007;158(2–3):224–36. https://doi.org/10.1016/j.resp.2007.03.005 Price, E. L., Vieira, J. M., & Riley, P. R. (2019). Model organisms at the heart of regeneration. Disease models & mechanisms, 12(10), dmm040691. https://doi.org/10.1242/dmm.040691 Richardson, W. J., Clarke, S. A., Quinn, T. A., & Holmes, J. W. (2015). Physiological Implications of Myocardial Scar Structure. Comprehensive Physiology, 5(4), 1877–1909. https://doi.org/10.1002/cphy.c140067 Rodríguez-Sinovas, A., Sánchez, J. A., Valls-Lacalle, L., Consegal, M., & Ferreira-González, I. (2021). Connexins in the Heart: Regulation, Function and Involvement in Cardiac Disease. International journal of molecular sciences, 22(9), 4413. https://doi.org/10.3390/ijms22094413 Sattar Y, Chhabra L. Electrocardiogram. [Updated 2023 Jun 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK549803/ Semenza, G. L. (2015, November 5). Dynamic regulation of stem cell specification and maintenance by hypoxia-inducible factors. Molecular Aspects of Medicine. https://www.sciencedirect.com/science/article/pii/S0098299715300030?via%3Dihub Sun, P., Zhang, Y., Yu, F., Parks, E., Lyman, A., Wu, Q., Ai, L., Hu, C. H., Zhou, Q., Shung, K., Lien, C. L., & Hsiai, T. K. (2009). Micro-electrocardiograms to study post-ventricular amputation of zebrafish heart. Annals of biomedical engineering, 37(5), 890–901. https://doi.org/10.1007/s10439-009-9668-3 Teame, T., Zhang, Z., Ran, C., Zhang, H., Yang, Y., Ding, Q., Xie, M., Gao, C., Ye, Y., Duan, M., & Zhou, Z. (2019). The use of zebrafish (Danio rerio) as biomedical models. Animal frontiers : the review magazine of animal agriculture, 9(3), 68–77. https://doi.org/10.1093/af/vfz020 Vornanen, M., & Hassinen, M. (2016). Zebrafish heart as a model for human cardiac electrophysiology. Channels (Austin, Tex.), 10(2), 101–110. https://doi.org/10.1080/19336950.2015.1121335 Zhao, Yali & Yun, Morgan & Nguyen, Sean & Tran, Michelle & Nguyen, Thao. (2019). In Vivo Surface Electrocardiography for Adult Zebrafish. Journal of Visualized Experiments. 10.3791/60011. |
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Garavito Aguilar, Zayra Vivianavirtual::22807-1Vásquez Vélez, Isabel Cristinavirtual::22806-1Arenas Pérez, CamiloFacultad de Ciencias::Laboratorio de Biología del desarrollo (Bioldes)2025-01-29T20:23:46Z2025-01-29T20:23:46Z2025-01-29https://hdl.handle.net/1992/75796instname:Universidad de los Andesreponame:Repositorio Institucional Sénecarepourl:https://repositorio.uniandes.edu.co/Cardiovascular diseases remain a leading cause of mortality globally. Heart failure often results in irreversible damage and the formation of non-contractile fibrotic scars that are not capable of proper electrical transmission as they are not an adequate substitute for cardiomyocytes. The scars are made of a non-contractile collagenous tissue that thins and compacts over time, increasing stress to the heart walls causing problems such as arrhythmias. Current research focuses on regenerative approaches to restore the lost cardiac tissue, using model organisms such as zebrafish (Danio rerio) due to their heart regeneration capacity, and similarities to humans in cell composition and electric activity. This study investigates the effects of hypobaric hypoxia on the regeneration processes as the hypoxia-inducible factors (HIF) have been seen to change cell metabolism, management of oxidative stress, and angiogenesis likely affecting heart electric activity. This was functionally visualized following the ventricular regeneration process after cryoinjury using electrocardiogram (ECG) analysis. Thus, we assess the cardiac electrical activity throughout the regeneration process of the zebrafish comparing a state of normoxia and a state of hypobaric hypoxia. All ECG data were processed through a principal component analysis, which revealed possible differences in cardiac recovery patterns between hypoxic and normoxic groups. Hypoxia-exposed zebrafish demonstrated potentially faster heart rate recovery, shorter RR intervals, likely influenced by chronic hypoxia adaptations such as enhanced HIF-1α expression and increased sympathetic nerve activity. These findings suggest that hypoxia could make the regeneration process more efficient, and prepare the heart for events of heart failure, which correlates with studies of humans permanently residing in high-altitude regions.This work was funded by the Universidad de los Andes (Bogotá – Colombia) through the seed project (INV-2021-126-2278), and by the Pontificia Universidad Javeriana (Bogotá – Colombia) – Vice-Rectorate of Research in the internal call for support of interdisciplinary research projects 2021 (project ID 20457).Pregrado21 páginasapplication/pdfengUniversidad de los AndesBiologíaFacultad de CienciasDepartamento de Ciencias BiológicasAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Evaluation of cardiac regeneration through electrocardiograms in Danio rerio in state of hypobaric hypoxiaTrabajo de grado - Pregradoinfo:eu-repo/semantics/bachelorThesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_7a1fTexthttp://purl.org/redcol/resource_type/TPHeart RegenerationElectrocardiogramHypoxiaNormoxiaDanio rerioHypobaric hypoxiaBiologíaArel, E., Rolland, L., Thireau, J., Torrente, AG., Bechard, E., Bride, J., Jopling, C., Demion, M., & Guennec, J.-Y. L. (2022, January 1). Characterization of the adult zebrafish electrocardiogram. bioRxiv. https://doi.org/10.1101/2022.02.02.478776Bo, B., Li, S., Zhou, K., & Wei, J. (2021). The Regulatory Role of Oxygen Metabolism in Exercise-Induced Cardiomyocyte Regeneration. Frontiers in cell and developmental biology, 9, 664527. https://doi.org/10.3389/fcell.2021.664527Bocchi, E. A., Arias, A., Verdejo, H., Diez, M., Gómez, E., Castro, P., & Interamerican Society of Cardiology (2013). The reality of heart failure in Latin America. Journal of the American College of Cardiology, 62(11), 949–958. https://doi.org/10.1016/j.jacc.2013.06.013Boron, W. F. & Boulpaep, E. L. Cardiac Electrophysiology and the Electrocardiogram. Medical Physiology (Third Edition, pp. 483–506). Elsevier. Retrieved 2024, from https://www-clinicalkey-com.ezproxy.uniandes.edu.co/#!/content/book/3-s2.0-B9781455743773000215.Burtscher M. (2013). Effects of living at higher altitudes on mortality: a narrative review. Aging and disease, 5(4), 274–280. https://doi.org/10.14336/AD.2014.0500274Burtscher, J., Citherlet, T., Camacho-Cardenosa, A., Camacho-Cardenosa, M., Raberin, A., Krumm, B., Hohenauer, E., Egg, M., Lichtblau, M., Müller, J., Rybnikova, E. A., Gatterer, H., Debevec, T., Baillieul, S., Manferdelli, G., Behrendt, T., Schega, L., Ehrenreich, H., Millet, G. P., Gassmann, M., … Mallet, R. T. (2024). Mechanisms underlying the health benefits of intermittent hypoxia conditioning. The Journal of physiology, 602(21), 5757–5783. https://doi.org/10.1113/JP285230Calbet, J. A., Robach, P., & Lundby, C. (2009). The exercising heart at altitude. Cellular and molecular life sciences : CMLS, 66(22), 3601–3613. https://doi.org/10.1007/s00018-009-0148-6Chablais, F., Veit, J., Rainer, G. et al. The zebrafish heart regenerates after cryoinjury-induced myocardial infarction. BMC Dev Biol 11, 21 (2011). https://doi.org/10.1186/1471-213X-11-21Dall, C., Khan, M., Chen, C.-A., & Angelos, M. G. (2016). Oxygen cycling to improve survival of stem cells for myocardial repair: A Review. Life Sciences, 153, 124–131. https://doi.org/10.1016/j.lfs.2016.04.011Dbouk, H. A., Mroue, R. M., El-Sabban, M. E., & Talhouk, R. S. (2009). Connexins: a myriad of functions extending beyond assembly of gap junction channels. Cell communication and signaling : CCS, 7, 4. https://doi.org/10.1186/1478-811X-7-4Ezzati, M., Murray Horwitz, M. E., Thomas, D. S., Friedman, A. B., Roach, R., Clark, T., Murray, C. J., & Honigman, B. (2012). Altitude, life expectancy and mortality from ischaemic heart disease, stroke, COPD and cancers: national population-based analysis of US counties. Journal of epidemiology and community health, 66(7), e17. https://doi.org/10.1136/jech.2010.112938Faeh D, Gutzwiller F, Bopp M. Lower mortality from coronary heart disease and stroke at higher altitudes in Switzerland. Circulation. 2009;120(6):495–501.Faulhaber, M., Gatterer, H., Haider, T., Linser, T., Netzer, N., & Burtscher, M. (2015). Heart rate and blood pressure responses during hypoxic cycles of a 3-week intermittent hypoxia breathing program in patients at risk for or with mild COPD. International journal of chronic obstructive pulmonary disease, 10, 339–345. https://doi.org/10.2147/COPD.S75749Gao, R., & Ren, J. (2021, July 20). Zebrafish models in therapeutic research of cardiac conduction disease. Frontiers. https://doi.org/10.3389/fcell.2021.731402Garbern, J. C., & Lee, R. T. (2022). Heart regeneration: 20 years of progress and renewed optimism. Developmental cell, 57(4), 424–439. https://doi.org/10.1016/j.devcel.2022.01.012González-Rosa, J. M., Burns, C. E., & Burns, C. G. (2017). Zebrafish heart regeneration: 15 years of discoveries. Regeneration (Oxford, England), 4(3), 105–123. https://doi.org/10.1002/reg2.83Hara H, Takeda N, Komuro I. Pathophysiology and therapeutic potential of cardiac fibrosis. Inflamm Regen. 2017;37(1):1–10Hochachka P. W. (1998). Mechanism and evolution of hypoxia-tolerance in humans. The Journal of experimental biology, 201(Pt 8), 1243–1254. https://doi.org/10.1242/jeb.201.8.1243Howe, K., Clark, M., Torroja, C. et al. (2013). The zebrafish reference genome sequence and its relationship to the human genome. Nature 496, 498–503. https://doi.org/10.1038/nature12111Johnson FL. Pathophysiology and Etiology of Heart Failure. Cardiol Clin [Internet]. 2014;32(1):9–19. Available from: http://dx.doi.org/10.1016/j.ccl.2013.09.015Jopling, C., Suñé, G., Faucherre, A., Fabregat, C., & Izpisua Belmonte, J. C. (2012). Hypoxia induces myocardial regeneration in zebrafish. Circulation, 126(25), 3017–3027. https://doi.org/10.1161/CIRCULATIONAHA.112.107888Kotini, M., Barriga, E.H., Leslie, J. et al. Gap junction protein Connexin-43 is a direct transcriptional regulator of N-cadherin in vivo. Nat Commun 9, 3846 (2018). https://doi.org/10.1038/s41467-018-06368-xMandic, M., Joyce, W., & Perry, S. F. (2021). 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