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Effects of fibrillin mutations on the behavior of heart muscle cells in Marfan syndrome

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Abstract
Marfan syndrome (MFS) is a systemic disorder of connective tissue caused by pathogenic variants in the fibrillin-1 (FBN1) gene. Myocardial dysfunction has been demonstrated in MFS patients and mouse models, but little is known about the intrinsic effect on the cardiomyocytes (CMs). In this study, both induced pluripotent stem cells derived from a MFS-patient and the line with the corrected FBN1 mutation were differentiated to CMs. Several functional analyses are performed on this model to study MFS related cardiomyopathy. Atomic force microscopy revealed that MFS CMs are stiffer compared to corrected CMs. The contraction amplitude of MFS CMs is decreased compared to corrected CMs. Under normal culture conditions, MFS CMs show a lower beat-to-beat variability compared to corrected CMs using multi electrode array. Isoproterenol-induced stress or cyclic strain demonstrates lack of support from the matrix in MFS CMs. This study reports the first cardiac cell culture model for MFS, revealing abnormalities in the behavior of MFS CMs that are related to matrix defects. Based on these results, we postulate that impaired support from the extracellular environment plays a key role in the improper functioning of CMs in MFS.
Keywords
PLURIPOTENT STEM-CELLS, BEAT RATE VARIABILITY, CARDIOVASCULAR MANIFESTATIONS, RECENT PROGRESS, MOUSE MODEL, CARDIOMYOPATHY, CARDIOMYOCYTES, PHENOTYPE, IPSC

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MLA
Aalders, Jeffrey, et al. “Effects of Fibrillin Mutations on the Behavior of Heart Muscle Cells in Marfan Syndrome.” SCIENTIFIC REPORTS, vol. 10, 2020, doi:10.1038/s41598-020-73802-w.
APA
Aalders, J., Léger, L., Van der Meeren, L., Van den Vreken, N., Skirtach, A., Sinha, S., … van Hengel, J. (2020). Effects of fibrillin mutations on the behavior of heart muscle cells in Marfan syndrome. SCIENTIFIC REPORTS, 10. https://doi.org/10.1038/s41598-020-73802-w
Chicago author-date
Aalders, Jeffrey, Laurens Léger, Louis Van der Meeren, Natasja Van den Vreken, Andre Skirtach, Sanjay Sinha, Julie De Backer, and Jolanda van Hengel. 2020. “Effects of Fibrillin Mutations on the Behavior of Heart Muscle Cells in Marfan Syndrome.” SCIENTIFIC REPORTS 10. https://doi.org/10.1038/s41598-020-73802-w.
Chicago author-date (all authors)
Aalders, Jeffrey, Laurens Léger, Louis Van der Meeren, Natasja Van den Vreken, Andre Skirtach, Sanjay Sinha, Julie De Backer, and Jolanda van Hengel. 2020. “Effects of Fibrillin Mutations on the Behavior of Heart Muscle Cells in Marfan Syndrome.” SCIENTIFIC REPORTS 10. doi:10.1038/s41598-020-73802-w.
Vancouver
1.
Aalders J, Léger L, Van der Meeren L, Van den Vreken N, Skirtach A, Sinha S, et al. Effects of fibrillin mutations on the behavior of heart muscle cells in Marfan syndrome. SCIENTIFIC REPORTS. 2020;10.
IEEE
[1]
J. Aalders et al., “Effects of fibrillin mutations on the behavior of heart muscle cells in Marfan syndrome,” SCIENTIFIC REPORTS, vol. 10, 2020.
@article{8677377,
  abstract     = {{Marfan syndrome (MFS) is a systemic disorder of connective tissue caused by pathogenic variants in the fibrillin-1 (FBN1) gene. Myocardial dysfunction has been demonstrated in MFS patients and mouse models, but little is known about the intrinsic effect on the cardiomyocytes (CMs). In this study, both induced pluripotent stem cells derived from a MFS-patient and the line with the corrected FBN1 mutation were differentiated to CMs. Several functional analyses are performed on this model to study MFS related cardiomyopathy. Atomic force microscopy revealed that MFS CMs are stiffer compared to corrected CMs. The contraction amplitude of MFS CMs is decreased compared to corrected CMs. Under normal culture conditions, MFS CMs show a lower beat-to-beat variability compared to corrected CMs using multi electrode array. Isoproterenol-induced stress or cyclic strain demonstrates lack of support from the matrix in MFS CMs. This study reports the first cardiac cell culture model for MFS, revealing abnormalities in the behavior of MFS CMs that are related to matrix defects. Based on these results, we postulate that impaired support from the extracellular environment plays a key role in the improper functioning of CMs in MFS.}},
  articleno    = {{16756}},
  author       = {{Aalders, Jeffrey and Léger, Laurens and Van der Meeren, Louis and Van den Vreken, Natasja and Skirtach, Andre and Sinha, Sanjay and De Backer, Julie and van Hengel, Jolanda}},
  issn         = {{2045-2322}},
  journal      = {{SCIENTIFIC REPORTS}},
  keywords     = {{PLURIPOTENT STEM-CELLS,BEAT RATE VARIABILITY,CARDIOVASCULAR MANIFESTATIONS,RECENT PROGRESS,MOUSE MODEL,CARDIOMYOPATHY,CARDIOMYOCYTES,PHENOTYPE,IPSC}},
  language     = {{eng}},
  pages        = {{16}},
  title        = {{Effects of fibrillin mutations on the behavior of heart muscle cells in Marfan syndrome}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-73802-w}},
  volume       = {{10}},
  year         = {{2020}},
}

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