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1. Author Correction: A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration

Author

Raso, Andrea, Dirkx, Ellen, Sampaio-Pinto, Vasco, el Azzouzi, Hamid, Cubero, Ryan J., Sorensen, Daniel W., Ottaviani, Lara, Olieslagers, Servé, Huibers, Manon M., de Weger, Roel, Siddiqi, Sailay, Moimas, Silvia, Torrini, Consuelo, Zentillin, Lorena, Braga, Luca, Nascimento, Diana S., da Costa Martins, Paula A., van Berlo, Jop H., Zacchigna, Serena, Giacca, Mauro, and De Windt, Leon J.

Published
2022
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3. Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs

Author

Experimentele Afd. Cardiologie 2, Regenerative Medicine and Stem Cells, Orthopaedie Onderzoek, Team Medisch, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Onderzoek Algemene Cardiologie, Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J, Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A, Serra, Margarida, Voets, Ilja K, Malda, Jos, Castilho, Miguel, van Laake, Linda W, Sluijter, Joost P G, Sampaio-Pinto, Vasco, van Mil, Alain, Experimentele Afd. Cardiologie 2, Regenerative Medicine and Stem Cells, Orthopaedie Onderzoek, Team Medisch, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Onderzoek Algemene Cardiologie, Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J, Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A, Serra, Margarida, Voets, Ilja K, Malda, Jos, Castilho, Miguel, van Laake, Linda W, Sluijter, Joost P G, Sampaio-Pinto, Vasco, and van Mil, Alain

Published
2024

4. Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs

Author

Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J, Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A, Serra, Margarida, Voets, Ilja K, Malda, Jos, Castilho, Miguel, van Laake, Linda W, Sluijter, Joost P G, Sampaio-Pinto, Vasco, van Mil, Alain, Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J, Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A, Serra, Margarida, Voets, Ilja K, Malda, Jos, Castilho, Miguel, van Laake, Linda W, Sluijter, Joost P G, Sampaio-Pinto, Vasco, and van Mil, Alain

Abstract

Cardiac tissue engineering (cTE) has already advanced towards the first clinical trials, investigating safety and feasibility of cTE construct transplantation in failing hearts. However, the lack of well-established preservation methods poses a hindrance to further scalability, commercialization, and transportation, thereby reducing their clinical implementation. In this study, hypothermic preservation (4 °C) and two methods for cryopreservation ( i.e., a slow and fast cooling approach to -196 °C and -150 °C, respectively) were investigated as potential solutions to extend the cTE construct implantation window. The cTE model used consisted of human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts embedded in a natural-derived hydrogel and supported by a polymeric melt electrowritten hexagonal scaffold. Constructs, composed of cardiomyocytes of different maturity, were preserved for three days, using several commercially available preservation protocols and solutions. Cardiomyocyte viability, function (beat rate and calcium handling), and metabolic activity were investigated after rewarming. Our observations show that cardiomyocytes' age did not influence post-rewarming viability, however, it influenced construct function. Hypothermic preservation with HypoThermosol® ensured cardiomyocyte viability and function. Furthermore, fast freezing outperformed slow freezing, but both viability and function were severely reduced after rewarming. In conclusion, whereas long-term preservation remains a challenge, hypothermic preservation with HypoThermosol® represents a promising solution for cTE construct short-term preservation and potential transportation, aiding in off-the-shelf availability, ultimately increasing their clinical applicability.

Published
2024

5. A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration

Author

Raso, Andrea, Dirkx, Ellen, Sampaio-Pinto, Vasco, el Azzouzi, Hamid, Cubero, Ryan J., Sorensen, Daniel W., Ottaviani, Lara, Olieslagers, Servé, Huibers, Manon M., de Weger, Roel, Siddiqi, Sailay, Moimas, Silvia, Torrini, Consuelo, Zentillin, Lorena, Braga, Luca, Nascimento, Diana S., da Costa Martins, Paula A., van Berlo, Jop H., Zacchigna, Serena, Giacca, Mauro, and De Windt, Leon J.

Published
2021
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8. Corrigendum: Consistent long-term therapeutic efficacy of human umbilical cord matrix-derived mesenchymal stromal cells after myocardial infarction despite individual differences and transient engraftment

Author

Laundos, Tiago L., primary, Vasques-Nóvoa, Francisco, additional, Gomes, Rita N., additional, Sampaio-Pinto, Vasco, additional, Cruz, Pedro, additional, Cruz, Hélder, additional, Santos, Jorge M., additional, Barcia, Rita N., additional, Pinto-do-Ó, Perpétua, additional, and Nascimento, Diana S., additional

Published
2023
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10. Generation, High-Throughput Screening, and Biobanking of Human-Induced Pluripotent Stem Cell-Derived Cardiac Spheroids

Author

Onderzoek Cardiovasculair Reg. Med., Experimentele Afd. Cardiologie 2, Team Onderzoek, Circulatory Health, Team Medisch, Regenerative Medicine and Stem Cells, Maas, Renee G C, Beekink, Tess, Chirico, Nino, Snijders Blok, Christian J B, Dokter, Inge, Sampaio-Pinto, Vasco, van Mil, Alain, Doevendans, Pieter A, Buikema, Jan W, Sluijter, Joost P G, Stillitano, Francesca, Onderzoek Cardiovasculair Reg. Med., Experimentele Afd. Cardiologie 2, Team Onderzoek, Circulatory Health, Team Medisch, Regenerative Medicine and Stem Cells, Maas, Renee G C, Beekink, Tess, Chirico, Nino, Snijders Blok, Christian J B, Dokter, Inge, Sampaio-Pinto, Vasco, van Mil, Alain, Doevendans, Pieter A, Buikema, Jan W, Sluijter, Joost P G, and Stillitano, Francesca

Published
2023

11. Hypothermic and cryogenic preservation of cardiac tissue-engineered constructsElectronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d3bm01908j

Author

Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J., Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A., Serra, Margarida, Voets, Ilja K., Malda, Jos, Castilho, Miguel, van Laake, Linda W., Sluijter, Joost P. G., Sampaio-Pinto, Vasco, and van Mil, Alain

Abstract

Cardiac tissue engineering (cTE) has already advanced towards the first clinical trials, investigating safety and feasibility of cTE construct transplantation in failing hearts. However, the lack of well-established preservation methods poses a hindrance to further scalability, commercialization, and transportation, thereby reducing their clinical implementation. In this study, hypothermic preservation (4 °C) and two methods for cryopreservation (i.e., a slow and fast cooling approach to −196 °C and −150 °C, respectively) were investigated as potential solutions to extend the cTE construct implantation window. The cTE model used consisted of human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts embedded in a natural-derived hydrogel and supported by a polymeric melt electrowritten hexagonal scaffold. Constructs, composed of cardiomyocytes of different maturity, were preserved for three days, using several commercially available preservation protocols and solutions. Cardiomyocyte viability, function (beat rate and calcium handling), and metabolic activity were investigated after rewarming. Our observations show that cardiomyocytes’ age did not influence post-rewarming viability, however, it influenced construct function. Hypothermic preservation with HypoThermosol® ensured cardiomyocyte viability and function. Furthermore, fast freezing outperformed slow freezing, but both viability and function were severely reduced after rewarming. In conclusion, whereas long-term preservation remains a challenge, hypothermic preservation with HypoThermosol® represents a promising solution for cTE construct short-term preservation and potential transportation, aiding in off-the-shelf availability, ultimately increasing their clinical applicability.

Published
2024
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12. Dissecting mechanisms of neonatal cardiac regeneration

Author

Sampaio Pinto, Vasco, Sampaio Pinto, Vasco, Sampaio Pinto, Vasco, and Sampaio Pinto, Vasco

Abstract

Cardiovascular diseases are the leading cause of death worldwide. After a heart attack, cardiac muscle dies, which progressively leads to organ dysfunction and heart failure. Current therapies focus on slowing disease progression but are not curative as they fail to restore the lost muscle. This thesis established and characterized an animal model of cardiac injury, where observe partial cardiac regeneration was observed, with restoration of cardiac muscle by division of cardiomyocytes, the contractile cells of the heart. This represents an important advance for cardiovascular research as it may contribute to the development of improved therapies. Moreover, an optimized protocol was developed to unequivocally quantify cardiomyocyte division. This protocol is now available to the scientific community and can be used by those willing to study activation of cardiac regenerative mechanisms and is expected to contribute to the identification of processes leading to the remuscularization of the heart after injury.

Published
2021

13. Intercellular transfer of miR-200c-3p impairs the angiogenic capacity of cardiac endothelial cells

Author

Ottaviani, Lara, primary, Juni, Rio P., additional, de Abreu, Ricardo C., additional, Sansonetti, Marida, additional, Sampaio-Pinto, Vasco, additional, Halkein, Julie, additional, Hegenbarth, Jana C., additional, Ring, Nadja, additional, Knoops, Kevin, additional, Kocken, Jordy M.M., additional, Jesus, Carlos de, additional, Ernault, Auriane C., additional, el Azzouzi, Hamid, additional, Rühle, Frank, additional, Olieslagers, Servé, additional, Fernandes, Hugo, additional, Ferreira, Lino, additional, Braga, Luca, additional, Stoll, Monika, additional, Nascimento, Diana S., additional, de Windt, Leon J., additional, and da Costa Martins, Paula A., additional

Published
2022
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14. Circadian Dependence of the Acute Immune Response to Myocardial Infarction

Author

Kilgallen, Aoife B., van den Akker, Frederieke, Feyen, Dries A.M., Crnko, Sandra, Snijders Blok, Christian J.B., Gremmels, Hendrik, du Pré, Bastiaan C., Reijers, Robin, Doevendans, Pieter A., de Jager, Saskia C.A., Sluijter, Joost P.G., Sampaio-Pinto, Vasco, van Laake, Linda W., Kilgallen, Aoife B., van den Akker, Frederieke, Feyen, Dries A.M., Crnko, Sandra, Snijders Blok, Christian J.B., Gremmels, Hendrik, du Pré, Bastiaan C., Reijers, Robin, Doevendans, Pieter A., de Jager, Saskia C.A., Sluijter, Joost P.G., Sampaio-Pinto, Vasco, and van Laake, Linda W.

Abstract

Circadian rhythms influence the recruitment of immune cells and the onset of inflammation, which is pivotal in the response to ischemic cardiac injury after a myocardial infarction (MI). The hyperacute immune response that occurs within the first few hours after a MI has not yet been elucidated. Therefore, we characterized the immune response and myocardial damage 3 hours after a MI occurs over a full twenty-four-hour period to investigate the role of the circadian rhythms in this response. MI was induced at Zeitgeber Time (ZT) 2, 8, 14, and 20 by permanent ligation of the left anterior descending coronary artery. Three hours after surgery, animals were terminated and blood and hearts collected to assess the immunological status and cardiac damage. Blood leukocyte numbers varied throughout the day, peaking during the rest-phase (ZT2 and 8). Extravasation of leukocytes was more pronounced during the active-phase (ZT14 and 20) and was associated with greater chemokine release to the blood and expression of adhesion molecules in the heart. Damage to the heart, measured by Troponin-I plasma levels, was elevated during this time frame. Clock gene oscillations remained intact in both MI-induced and sham-operated mice hearts, which could explain the circadian influence of the hyperacute inflammatory response after a MI. These findings are in line with the clinical observation that patients who experience a MI early in the morning (i.e., early active phase) have worse clinical outcomes. This study provides further insight on the immune response occurring shortly after an MI, which may contribute to the development of novel and optimization of current therapeutic approaches.

Published
2022

15. Author Correction: A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration (Nature Communications, (2021), 12, 1, (4808), 10.1038/s41467-021-25211-4)

Author

Pathologie patiënten zorg, Genetica Sectie Genoomdiagnostiek, Pathologie Laboratorium diagnostiek, Raso, Andrea, Dirkx, Ellen, Sampaio-Pinto, Vasco, el Azzouzi, Hamid, Cubero, Ryan J., Sorensen, Daniel W., Ottaviani, Lara, Olieslagers, Servé, Huibers, Manon M., de Weger, Roel, Siddiqi, Sailay, Moimas, Silvia, Torrini, Consuelo, Zentillin, Lorena, Braga, Luca, Nascimento, Diana S., da Costa Martins, Paula A., van Berlo, Jop H., Zacchigna, Serena, Giacca, Mauro, De Windt, Leon J., Pathologie patiënten zorg, Genetica Sectie Genoomdiagnostiek, Pathologie Laboratorium diagnostiek, Raso, Andrea, Dirkx, Ellen, Sampaio-Pinto, Vasco, el Azzouzi, Hamid, Cubero, Ryan J., Sorensen, Daniel W., Ottaviani, Lara, Olieslagers, Servé, Huibers, Manon M., de Weger, Roel, Siddiqi, Sailay, Moimas, Silvia, Torrini, Consuelo, Zentillin, Lorena, Braga, Luca, Nascimento, Diana S., da Costa Martins, Paula A., van Berlo, Jop H., Zacchigna, Serena, Giacca, Mauro, and De Windt, Leon J.

Published
2022

16. Circadian Dependence of the Acute Immune Response to Myocardial Infarction

Author

Experimentele Afd. Cardiologie 2, Pathologie Bachelor Research hub, MMB opleiding Arts microbioloog, Infection & Immunity, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Onderzoek Cardiovasculair Reg. Med., Team Onderzoek, Kilgallen, Aoife B, van den Akker, Frederieke, Feyen, Dries A M, Crnko, Sandra, Snijders Blok, Christian J B, Gremmels, Hendrik, du Pré, Bastiaan C, Reijers, Robin, Doevendans, Pieter A, de Jager, Saskia C A, Sluijter, Joost P G, Sampaio-Pinto, Vasco, van Laake, Linda W, Experimentele Afd. Cardiologie 2, Pathologie Bachelor Research hub, MMB opleiding Arts microbioloog, Infection & Immunity, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Onderzoek Cardiovasculair Reg. Med., Team Onderzoek, Kilgallen, Aoife B, van den Akker, Frederieke, Feyen, Dries A M, Crnko, Sandra, Snijders Blok, Christian J B, Gremmels, Hendrik, du Pré, Bastiaan C, Reijers, Robin, Doevendans, Pieter A, de Jager, Saskia C A, Sluijter, Joost P G, Sampaio-Pinto, Vasco, and van Laake, Linda W

Published
2022

17. Circadian Dependence of the Acute Immune Response to Myocardial Infarction

Author

Kilgallen, Aoife B., primary, van den Akker, Frederieke, additional, Feyen, Dries A. M., additional, Crnko, Sandra, additional, Snijders Blok, Christian J. B., additional, Gremmels, Hendrik, additional, du Pré, Bastiaan C., additional, Reijers, Robin, additional, Doevendans, Pieter A., additional, de Jager, Saskia C. A., additional, Sluijter, Joost P. G., additional, Sampaio-Pinto, Vasco, additional, and van Laake, Linda W., additional

Published
2022
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18. Pharmacological clearance of senescent cells reverses HFpEF hallmarks by decreasing inflammation, endothelial dysfunction and cardiac fibrosis

Author

Silva, Elsa, primary, Tomé, Inês, additional, Vasques-Nóvoa, Francisco, additional, Conceição, Glória, additional, Silva, Andreia, additional, Barros, António, additional, Angélico-Gonçalves, António, additional, Caetano, Carolina, additional, Sousa, Daniel, additional, Miranda-Silva, Daniela, additional, Gonçalves, Nádia, additional, Sampaio-Pinto, Vasco, additional, Gonçalves, Alexandre, additional, Leite-Moreira, Adelino, additional, Falcão-Pires, Inês, additional, Pitrez, Patrícia, additional, Pinto-do-Ó, Perpétua, additional, Santos, Susana, additional, Ferreira, Lino, additional, and Nascimento, Diana, additional

Published
2021
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21. A Roadmap to Cardiac Tissue-Engineered Construct Preservation: Insights from Cells, Tissues, and Organs

Author

Sampaio-Pinto, Vasco, Janssen, Jasmijn, Chirico, Nino, Serra, Margarida, Alves, Paula M., Doevendans, Pieter A., Voets, Ilja K., Sluijter, Joost P.G., van Laake, Linda W., van Mil, Alain, Sampaio-Pinto, Vasco, Janssen, Jasmijn, Chirico, Nino, Serra, Margarida, Alves, Paula M., Doevendans, Pieter A., Voets, Ilja K., Sluijter, Joost P.G., van Laake, Linda W., and van Mil, Alain

Abstract

Worldwide, over 26 million patients suffer from heart failure (HF). One strategy aspiring to prevent or even to reverse HF is based on the transplantation of cardiac tissue-engineered (cTE) constructs. These patient-specific constructs aim to closely resemble the native myocardium and, upon implantation on the diseased tissue, support and restore cardiac function, thereby preventing the development of HF. However, cTE constructs off-the-shelf availability in the clinical arena critically depends on the development of efficient preservation methodologies. Short- and long-term preservation of cTE constructs would enable transportation and direct availability. Herein, currently available methods, from normothermic- to hypothermic- to cryopreservation, for the preservation of cardiomyocytes, whole-heart, and regenerative materials are reviewed. A theoretical foundation and recommendations for future research on developing cTE construct specific preservation methods are provided. Current research suggests that vitrification can be a promising procedure to ensure long-term cryopreservation of cTE constructs, despite the need of high doses of cytotoxic cryoprotective agents. Instead, short-term cTE construct preservation can be achieved at normothermic or hypothermic temperatures by administration of protective additives. With further tuning of these promising methods, it is anticipated that cTE construct therapy can be brought one step closer to the patient.

Published
2021

22. A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration

Author

Pathologie Algemene Pat.zorg, Genetica Sectie Genoomdiagnostiek, Raso, Andrea, Dirkx, Ellen, Sampaio-Pinto, Vasco, el Azzouzi, Hamid, Cubero, Ryan J., Sorensen, Daniel W., Ottaviani, Lara, Olieslagers, Servé, Huibers, Manon M., de Weger, Roel, Siddiqi, Sailay, Moimas, Silvia, Torrini, Consuelo, Zentillin, Lorena, Braga, Luca, Nascimento, Diana S., da Costa Martins, Paula A., van Berlo, Jop H., Zacchigna, Serena, Giacca, Mauro, De Windt, Leon J., Pathologie Algemene Pat.zorg, Genetica Sectie Genoomdiagnostiek, Raso, Andrea, Dirkx, Ellen, Sampaio-Pinto, Vasco, el Azzouzi, Hamid, Cubero, Ryan J., Sorensen, Daniel W., Ottaviani, Lara, Olieslagers, Servé, Huibers, Manon M., de Weger, Roel, Siddiqi, Sailay, Moimas, Silvia, Torrini, Consuelo, Zentillin, Lorena, Braga, Luca, Nascimento, Diana S., da Costa Martins, Paula A., van Berlo, Jop H., Zacchigna, Serena, Giacca, Mauro, and De Windt, Leon J.

Published
2021

24. A Roadmap to Cardiac Tissue-Engineered Construct Preservation: Insights from Cells, Tissues, and Organs

Author

Team Onderzoek, Regenerative Medicine and Stem Cells, Experimentele Afd. Cardiologie 2, Team Medisch, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Sampaio-Pinto, Vasco, Janssen, Jasmijn, Chirico, Nino, Serra, Margarida, Alves, Paula M, Doevendans, Pieter A, Voets, Ilja K, Sluijter, Joost P G, van Laake, Linda W, van Mil, Alain, Team Onderzoek, Regenerative Medicine and Stem Cells, Experimentele Afd. Cardiologie 2, Team Medisch, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Sampaio-Pinto, Vasco, Janssen, Jasmijn, Chirico, Nino, Serra, Margarida, Alves, Paula M, Doevendans, Pieter A, Voets, Ilja K, Sluijter, Joost P G, van Laake, Linda W, and van Mil, Alain

Published
2021

28. A microRNA program controls the transition of cardiomyocyte hyperplasia to hypertrophy and stimulates mammalian cardiac regeneration

Author

Raso, Andrea, primary, Dirkx, Ellen, additional, Sampaio-Pinto, Vasco, additional, el Azzouzi, Hamid, additional, Cubero, Ryan J., additional, Sorensen, Daniel W., additional, Ottaviani, Lara, additional, Olieslagers, Servé, additional, Huibers, Manon M., additional, de Weger, Roel, additional, Siddiqi, Sailay, additional, Moimas, Silvia, additional, Torrini, Consuelo, additional, Zentillin, Lorena, additional, Braga, Luca, additional, da Costa Martins, Paula A., additional, van Berlo, Jop H., additional, Zacchigna, Serena, additional, Giacca, Mauro, additional, and De Windt, Leon J., additional

Published
2021
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29. Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment

Author

Laundos, Tiago L., primary, Vasques-Nóvoa, Francisco, additional, Gomes, Rita N., additional, Sampaio-Pinto, Vasco, additional, Cruz, Pedro, additional, Cruz, Hélder, additional, Santos, Jorge M., additional, Barcia, Rita N., additional, Pinto-do-Ó, Perpétua, additional, and Nascimento, Diana S., additional

Published
2021
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31. Therapeutic Delivery of miR-148a Suppresses Ventricular Dilation in Heart Failure

Author

Raso, Andrea, Dirkx, Ellen, Philippen, Leonne E, Fernandez-Celis, Amaya, De Majo, Federica, Sampaio-Pinto, Vasco, Sansonetti, Marida, Juni, Rio, El Azzouzi, Hamid, Calore, Martina, Bitsch, Nicole, Olieslagers, Servé, Oerlemans, Martinus I F J, Huibers, Manon M, de Weger, Roel A, Reckman, Yolan J, Pinto, Yigal M, Zentilin, Lorena, Zacchigna, Serena, Giacca, Mauro, da Costa Martins, Paula A, López-Andrés, Natalia, De Windt, Leon J, Raso, Andrea, Dirkx, Ellen, Philippen, Leonne E, Fernandez-Celis, Amaya, De Majo, Federica, Sampaio-Pinto, Vasco, Sansonetti, Marida, Juni, Rio, El Azzouzi, Hamid, Calore, Martina, Bitsch, Nicole, Olieslagers, Servé, Oerlemans, Martinus I F J, Huibers, Manon M, de Weger, Roel A, Reckman, Yolan J, Pinto, Yigal M, Zentilin, Lorena, Zacchigna, Serena, Giacca, Mauro, da Costa Martins, Paula A, López-Andrés, Natalia, and De Windt, Leon J

Published
2019

32. Therapeutic Delivery of miR-148a Suppresses Ventricular Dilation in Heart Failure

Author

Onderzoek Cardiovasculair Reg. Med., Team Medisch, Pathologie Laboratorium diagnostiek, Cancer, Circulatory Health, Raso, Andrea, Dirkx, Ellen, Philippen, Leonne E, Fernandez-Celis, Amaya, De Majo, Federica, Sampaio-Pinto, Vasco, Sansonetti, Marida, Juni, Rio, El Azzouzi, Hamid, Calore, Martina, Bitsch, Nicole, Olieslagers, Servé, Oerlemans, Martinus I F J, Huibers, Manon M, de Weger, Roel A, Reckman, Yolan J, Pinto, Yigal M, Zentilin, Lorena, Zacchigna, Serena, Giacca, Mauro, da Costa Martins, Paula A, López-Andrés, Natalia, De Windt, Leon J, Onderzoek Cardiovasculair Reg. Med., Team Medisch, Pathologie Laboratorium diagnostiek, Cancer, Circulatory Health, Raso, Andrea, Dirkx, Ellen, Philippen, Leonne E, Fernandez-Celis, Amaya, De Majo, Federica, Sampaio-Pinto, Vasco, Sansonetti, Marida, Juni, Rio, El Azzouzi, Hamid, Calore, Martina, Bitsch, Nicole, Olieslagers, Servé, Oerlemans, Martinus I F J, Huibers, Manon M, de Weger, Roel A, Reckman, Yolan J, Pinto, Yigal M, Zentilin, Lorena, Zacchigna, Serena, Giacca, Mauro, da Costa Martins, Paula A, López-Andrés, Natalia, and De Windt, Leon J

Published
2019

34. Therapeutic Delivery of miR-148a Suppresses Ventricular Dilation in Heart Failure

Author

Raso, Andrea, primary, Dirkx, Ellen, additional, Philippen, Leonne E., additional, Fernandez-Celis, Amaya, additional, De Majo, Federica, additional, Sampaio-Pinto, Vasco, additional, Sansonetti, Marida, additional, Juni, Rio, additional, el Azzouzi, Hamid, additional, Calore, Martina, additional, Bitsch, Nicole, additional, Olieslagers, Servé, additional, Oerlemans, Martinus I.F.J., additional, Huibers, Manon M., additional, de Weger, Roel A., additional, Reckman, Yolan J., additional, Pinto, Yigal M., additional, Zentilin, Lorena, additional, Zacchigna, Serena, additional, Giacca, Mauro, additional, da Costa Martins, Paula A., additional, López-Andrés, Natalia, additional, and De Windt, Leon J., additional

Published
2019
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35. Neonatal Apex Resection Triggers Cardiomyocyte Proliferation, Neovascularization and Functional Recovery Despite Local Fibrosis

Author

Sampaio-Pinto, Vasco, primary, Rodrigues, Sílvia C., additional, Laundos, Tiago L., additional, Silva, Elsa D., additional, Vasques-Nóvoa, Francisco, additional, Silva, Ana C., additional, Cerqueira, Rui J., additional, Resende, Tatiana P., additional, Pianca, Nicola, additional, Leite-Moreira, Adelino, additional, D'Uva, Gabriele, additional, Thorsteinsdóttir, Sólveig, additional, Pinto-do-Ó, Perpétua, additional, and Nascimento, Diana S., additional

Published
2018
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36. Establishing a Link between Endothelial Cell Metabolism and Vascular Behaviour in a Type 1 Diabetes Mouse Model.

Author

Silva, Carolina, Sampaio-Pinto, Vasco, Andrade, Sara, Rodrigues, Ilda, Costa, Raquel, Guerreiro, Susana, Carvalho, Eugenia, Pinto-do-Ó, Perpétua, Nascimento, Diana S., and Soares, Raquel

Subjects
*ENDOTHELIAL cells, *TYPE 1 diabetes, *NEOVASCULARIZATION, *GENE expression, *PROTEIN kinases, *IMMUNOHISTOCHEMISTRY
Abstract

Background/Aims: Vascular complications contribute significantly to the extensive morbidity and mortality rates observed in people with diabetes. Despite well known that the diabetic kidney and heart exhibit imbalanced angiogenesis, the mechanisms implicated in this angiogenic paradox remain unknown. In this study, we examined the angiogenic and metabolic gene expression profile (GEP) of endothelial cells (ECs) isolated from a mouse model with type1 diabetes mellitus (T1DM). Methods: ECs were isolated from kidneys and hearts of healthy and streptozocin (STZ)-treated mice. RNA was then extracted for molecular studies. GEP of 84 angiogenic and 84 AMP-activated Protein Kinase (AMPK)-dependent genes were examined by microarrays. Real time PCR confirmed the changes observed in significantly altered genes. Microvessel density (MVD) was analysed by immunohistochemistry, fibrosis was assessed by the Sirius red histological staining and connective tissue growth factor (CTGF) was quantified by ELISA. Results: The relative percentage of ECs and MVD were increased in the kidneys of T1DM animals whereas the opposite trend was observed in the hearts of diabetic mice. Accordingly, the majority of AMPK-associated genes were upregulated in kidneys and downregulated in hearts of these animals. Angiogenic GEP revealed significant differences in Tgfβ, Notch signaling and Timp2 in both diabetic organs. These findings were in agreement with the angiogenesis histological assays. Fibrosis was augmented in both organs in diabetic as compared to healthy animals. Conclusion: Altogether, our findings indicate, for the first time, that T1DM heart and kidney ECs present opposite metabolic cues, which are accompanied by distinct angiogenic patterns. These findings enable the development of innovative organ-specific therapeutic strategies targeting diabetic-associated vascular disorders. [ABSTRACT FROM AUTHOR]

Published
2019
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38. Therapeutic Delivery of miR-148a Suppresses Ventricular Dilation in Heart Failure

Author

Mauro Giacca, Hamid el Azzouzi, Lorena Zentilin, Martinus I. F. J. Oerlemans, Natalia López-Andrés, Yigal M. Pinto, Paula A. da Costa Martins, Serena Zacchigna, Manon M. H. Huibers, Marida Sansonetti, Martina Calore, Andrea Raso, Roel A. de Weger, Leon J. De Windt, Amaya Fernández-Celis, Leonne E Philippen, Rio P. Juni, Nicole Bitsch, Federica De Majo, Servé Olieslagers, Ellen Dirkx, Vasco Sampaio-Pinto, Yolan J. Reckman, Raso, Andrea, Dirkx, Ellen, Philippen, Leonne E., Fernandez-Celis, Amaya, De Majo, Federica, Sampaio-Pinto, Vasco, Sansonetti, Marida, Juni, Rio, el Azzouzi, Hamid, Calore, Martina, Bitsch, Nicole, Olieslagers, Servé, Oerlemans, Martinus I. F. J., Huibers, Manon M., de Weger, Roel A., Reckman, Yolan J., Pinto, Yigal M., Zentilin, Lorena, Zacchigna, Serena, Giacca, Mauro, da Costa Martins, Paula A., López-Andrés, Natalia, De Windt, Leon J., Cardiologie, RS: CARIM - R2 - Cardiac function and failure, RS: CARIM - R2.07 - Gene regulation, Promovendi CD, RS: FSE DMG, Ondersteunend personeel CD, RS: Carim - Heart, RS: Carim - H05 Gene regulation, RS: CARIM School for Cardiovascular Diseases, Cardiology, Graduate School, ACS - Heart failure & arrhythmias, Physiology, and ACS - Microcirculation

Subjects
adeno-associated vector, cardiac, heart failure, hypertrophy, microRNA, miR-148a, signaling, Molecular Medicine, Molecular Biology, Genetics, Pharmacology, Drug Discovery3003 Pharmaceutical Science, Volume overload, Muscle hypertrophy, Mice, 0302 clinical medicine, Drug Discovery, Medicine, CARDIAC-HYPERTROPHY, IN-VIVO, 0303 health sciences, Ejection fraction, Ventricular Remodeling, GP130, Dilated cardiomyopathy, 3. Good health, BRAIN NATRIURETIC PEPTIDE, 030220 oncology & carcinogenesis, SURVIVAL, Cardiology, Original Article, Cardiomyopathies, Signal Transduction, STAT3 Transcription Factor, EXPRESSION, INTERLEUKIN-6 FAMILY, medicine.medical_specialty, Concentric hypertrophy, Cardiomegaly, MYOCYTES, 03 medical and health sciences, Genetic, Internal medicine, Journal Article, Animals, Humans, PLASMA CARDIOTROPHIN-1, Ventricular remodeling, Cell Proliferation, 030304 developmental biology, Pressure overload, business.industry, Myocardium, medicine.disease, Dilatation, GENE, MicroRNAs, Heart failure, Commentary, Heart Transplantation, business
Abstract

Heart failure is preceded by ventricular remodeling, changes in left ventricular mass, and myocardial volume after alterations in loading conditions. Concentric hypertrophy arises after pressure overload, involves wall thickening, and forms a substrate for diastolic dysfunction. Eccentric hypertrophy develops in volume overload conditions and leads wall thinning, chamber dilation, and reduced ejection fraction. The molecular events underlying these distinct forms of cardiac remodeling are poorly understood. Here, we demonstrate that miR-148a expression changes dynamically in distinct subtypes of heart failure: while it is elevated in concentric hypertrophy, it decreased in dilated cardiomyopathy. In line, antagomir-mediated silencing of miR-148a caused wall thinning, chamber dilation, increased left ventricle volume, and reduced ejection fraction. Additionally, adeno-associated viral delivery of miR-148a protected the mouse heart from pressure-overload-induced systolic dysfunction by preventing the transition of concentric hypertrophic remodeling toward dilation. Mechanistically, miR-148a targets the cytokine co-receptor glycoprotein 130 (gp130) and connects cardiomyocyte responsiveness to extracellular cytokines by modulating the Stat3 signaling. These findings show the ability of miR-148a to prevent the transition of pressure-overload induced concentric hypertrophic remodeling toward eccentric hypertrophy and dilated cardiomyopathy and provide evidence for the existence of separate molecular programs inducing distinct forms of myocardial remodeling., Raso et al. show that miR-148a is elevated in concentric hypertrophy and decreased in dilated cardiomyopathy. Adeno-associated viral delivery of miR-148a protects the mouse heart from cardiac dilation. Mechanistically, miR-148a regulates the sensitivity of the heart to extracellular cytokines.

Published
2019
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