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Mimicking Cardiac Fibrosis in a Dish: Fibroblast Density Rather Than Collagen Density Weakens Cardiomyocyte Function

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Publisher Springer
Date 2017 Mar 11
PMID 28281243
Citations 26
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Abstract

Cardiac fibrosis is one of the most devastating effects of cardiac disease. Current in vitro models of cardiac fibrosis do not sufficiently mimic the complex in vivo environment of the cardiomyocyte. We determined the local composition and mechanical properties of the myocardium in established mouse models of genetic and acquired fibrosis and tested the effect of myocardial composition on cardiomyocyte contractility in vitro by systematically manipulating the number of fibroblasts and collagen concentration in a platform of engineered cardiac microtissues. The in vitro results showed that while increasing collagen content had little effect on microtissue contraction, increasing fibroblast density caused a significant reduction in contraction force. In addition, the beating frequency dropped significantly in tissues consisting of 50% cardiac fibroblasts or higher. Despite apparent dissimilarities between native and in vitro fibrosis, the latter allows for the independent analysis of local determinants of fibrosis, which is not possible in vivo.

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References
1.
Verhaart I, van Duijn R, den Adel B, Roest A, Verschuuren J, Aartsma-Rus A . Assessment of cardiac function in three mouse dystrophinopathies by magnetic resonance imaging. Neuromuscul Disord. 2012; 22(5):418-26. DOI: 10.1016/j.nmd.2011.10.025. View

2.
Han L, Li Y, Tchao J, Kaplan A, Lin B, Li Y . Study familial hypertrophic cardiomyopathy using patient-specific induced pluripotent stem cells. Cardiovasc Res. 2014; 104(2):258-69. PMC: 4217687. DOI: 10.1093/cvr/cvu205. View

3.
Soares C, Midlej V, de Oliveira M, Benchimol M, Costa M, Mermelstein C . 2D and 3D-organized cardiac cells shows differences in cellular morphology, adhesion junctions, presence of myofibrils and protein expression. PLoS One. 2012; 7(5):e38147. PMC: 3360656. DOI: 10.1371/journal.pone.0038147. View

4.
Puttini S, Lekka M, Dorchies O, Saugy D, Incitti T, Ruegg U . Gene-mediated restoration of normal myofiber elasticity in dystrophic muscles. Mol Ther. 2008; 17(1):19-25. PMC: 2834969. DOI: 10.1038/mt.2008.239. View

5.
Chang M, Zhang Y, Chang C, Xu L, Emokpae R, Tung L . Spiral waves and reentry dynamics in an in vitro model of the healed infarct border zone. Circ Res. 2009; 105(11):1062-71. PMC: 4980100. DOI: 10.1161/CIRCRESAHA.108.176248. View