Extracellular matrix and cyclic stretch alter fetal cardiomyocyte proliferation and maturation in a rodent model of heart hypoplasia
IntroductionBirth defects, particularly those that affect development of the heart, are a leading cause of morbidity and mortality in infants and young children. Babies born with heart hypoplasia (heart hypoplasia) disorders often have a poor prognosis. It remains unclear whether cardiomyocytes from...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.993310/full |
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| author | Matthew C. Watson Matthew C. Watson Corin Williams Raymond M. Wang Luke R. Perreault Kelly E. Sullivan Whitney L. Stoppel Lauren D. Black Lauren D. Black |
| author_facet | Matthew C. Watson Matthew C. Watson Corin Williams Raymond M. Wang Luke R. Perreault Kelly E. Sullivan Whitney L. Stoppel Lauren D. Black Lauren D. Black |
| author_sort | Matthew C. Watson |
| collection | DOAJ |
| description | IntroductionBirth defects, particularly those that affect development of the heart, are a leading cause of morbidity and mortality in infants and young children. Babies born with heart hypoplasia (heart hypoplasia) disorders often have a poor prognosis. It remains unclear whether cardiomyocytes from hypoplastic hearts retain the potential to recover growth, although this knowledge would be beneficial for developing therapies for heart hypoplasia disorders. The objective of this study was to determine the proliferation and maturation potential of cardiomyocytes from hypoplastic hearts and whether these behaviors are influenced by biochemical signaling from the extracellular matrix (ECM) and cyclic mechanical stretch.MethodCongenital diaphragmatic hernia (CDH)-associated heart hypoplasia was induced in rat fetuses by maternal exposure to nitrofen. Hearts were isolated from embryonic day 21 nitrofen-treated fetuses positive for CDH (CDH+) and from fetuses without nitrofen administration during gestation.Results and discussionCDH+ hearts were smaller and had decreased myocardial proliferation, along with evidence of decreased maturity compared to healthy hearts. In culture, CDH+ cardiomyocytes remained immature and demonstrated increased proliferative capacity compared to their healthy counterparts. Culture on ECM derived from CDH+ hearts led to a significant reduction in proliferation for both CDH+ and healthy cardiomyocytes. Healthy cardiomyocytes were dosed with exogenous nitrofen to examine whether nitrofen may have an aberrant effect on the proliferative ability of cardiomyocyte, yet no significant change in proliferation was observed. When subjected to stretch, CDH+ cardiomyocytes underwent lengthening of sarcomeres while healthy cardiomyocyte sarcomeres were unaffected. Taken together, our results suggest that alterations to environmental cues such as ECM and stretch may be important factors in the pathological progression of heart hypoplasia. |
| first_indexed | 2024-04-12T05:03:37Z |
| format | Article |
| id | doaj.art-6b5a14ef36d54cf2910b64c81dff23ac |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-12T05:03:37Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-6b5a14ef36d54cf2910b64c81dff23ac2022-12-22T03:46:55ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-11-01910.3389/fcvm.2022.993310993310Extracellular matrix and cyclic stretch alter fetal cardiomyocyte proliferation and maturation in a rodent model of heart hypoplasiaMatthew C. Watson0Matthew C. Watson1Corin Williams2Raymond M. Wang3Luke R. Perreault4Kelly E. Sullivan5Whitney L. Stoppel6Lauren D. Black7Lauren D. Black8Department of Biomedical Engineering, Tufts University, Medford, MA, United StatesDepartment of Mechanical Engineering, Tufts University, Medford, MA, United StatesDepartment of Biomedical Engineering, Tufts University, Medford, MA, United StatesDepartment of Biomedical Engineering, Tufts University, Medford, MA, United StatesDepartment of Biomedical Engineering, Tufts University, Medford, MA, United StatesDepartment of Biomedical Engineering, Tufts University, Medford, MA, United StatesDepartment of Biomedical Engineering, Tufts University, Medford, MA, United StatesDepartment of Biomedical Engineering, Tufts University, Medford, MA, United StatesCellular, Molecular, and Developmental Biology Program, Sackler School for Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA, United StatesIntroductionBirth defects, particularly those that affect development of the heart, are a leading cause of morbidity and mortality in infants and young children. Babies born with heart hypoplasia (heart hypoplasia) disorders often have a poor prognosis. It remains unclear whether cardiomyocytes from hypoplastic hearts retain the potential to recover growth, although this knowledge would be beneficial for developing therapies for heart hypoplasia disorders. The objective of this study was to determine the proliferation and maturation potential of cardiomyocytes from hypoplastic hearts and whether these behaviors are influenced by biochemical signaling from the extracellular matrix (ECM) and cyclic mechanical stretch.MethodCongenital diaphragmatic hernia (CDH)-associated heart hypoplasia was induced in rat fetuses by maternal exposure to nitrofen. Hearts were isolated from embryonic day 21 nitrofen-treated fetuses positive for CDH (CDH+) and from fetuses without nitrofen administration during gestation.Results and discussionCDH+ hearts were smaller and had decreased myocardial proliferation, along with evidence of decreased maturity compared to healthy hearts. In culture, CDH+ cardiomyocytes remained immature and demonstrated increased proliferative capacity compared to their healthy counterparts. Culture on ECM derived from CDH+ hearts led to a significant reduction in proliferation for both CDH+ and healthy cardiomyocytes. Healthy cardiomyocytes were dosed with exogenous nitrofen to examine whether nitrofen may have an aberrant effect on the proliferative ability of cardiomyocyte, yet no significant change in proliferation was observed. When subjected to stretch, CDH+ cardiomyocytes underwent lengthening of sarcomeres while healthy cardiomyocyte sarcomeres were unaffected. Taken together, our results suggest that alterations to environmental cues such as ECM and stretch may be important factors in the pathological progression of heart hypoplasia.https://www.frontiersin.org/articles/10.3389/fcvm.2022.993310/fullcardiomyocytesproliferationheart hypoplasiaextracellular matrix (ECM)mechanical stretch |
| spellingShingle | Matthew C. Watson Matthew C. Watson Corin Williams Raymond M. Wang Luke R. Perreault Kelly E. Sullivan Whitney L. Stoppel Lauren D. Black Lauren D. Black Extracellular matrix and cyclic stretch alter fetal cardiomyocyte proliferation and maturation in a rodent model of heart hypoplasia Frontiers in Cardiovascular Medicine cardiomyocytes proliferation heart hypoplasia extracellular matrix (ECM) mechanical stretch |
| title | Extracellular matrix and cyclic stretch alter fetal cardiomyocyte proliferation and maturation in a rodent model of heart hypoplasia |
| title_full | Extracellular matrix and cyclic stretch alter fetal cardiomyocyte proliferation and maturation in a rodent model of heart hypoplasia |
| title_fullStr | Extracellular matrix and cyclic stretch alter fetal cardiomyocyte proliferation and maturation in a rodent model of heart hypoplasia |
| title_full_unstemmed | Extracellular matrix and cyclic stretch alter fetal cardiomyocyte proliferation and maturation in a rodent model of heart hypoplasia |
| title_short | Extracellular matrix and cyclic stretch alter fetal cardiomyocyte proliferation and maturation in a rodent model of heart hypoplasia |
| title_sort | extracellular matrix and cyclic stretch alter fetal cardiomyocyte proliferation and maturation in a rodent model of heart hypoplasia |
| topic | cardiomyocytes proliferation heart hypoplasia extracellular matrix (ECM) mechanical stretch |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.993310/full |
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