TY  - JOUR
AU  - Heras-Bautista, Carlos O.
AU  - Mikhael, Nelly
AU  - Lam, Jennifer
AU  - Shinde, Vaibhav
AU  - Katsen-Globa, Alisa
AU  - Dieluweit, Sabine
AU  - Molcanyi, Marek
AU  - Uvarov, Vladimir
AU  - Jütten, Peter
AU  - Sahito, Raja G. A.
AU  - Mederos-Henry, Francisco
AU  - Piechot, Alexander
AU  - Brockmeier, Konrad
AU  - Hescheler, Jürgen
AU  - Sachinidis, Agapios
AU  - Pfannkuche, Kurt
TI  - Cardiomyocytes facing fibrotic conditions re-express extracellular matrix transcripts7
JO  - Acta biomaterialia
VL  - 89
SN  - 1742-7061
CY  - [Amsterdam]
PB  - Elsevier
M1  - FZJ-2019-01964
SP  - 180-192
PY  - 2019
AB  - Pathophysiological conditions, such as myocardial infarction and mechanical overload affect the mammalian heart integrity, leading to a stiffened fibrotic tissue. With respect to the pathophysiology of cardiac fibrosis but also in the limelight of upcoming approaches of cardiac cell therapy it is of interest to decipher the interaction of cardiomyocytes with fibrotic matrix. Therefore, we designed a hydrogel-based model to engineer fibrotic tissue in vitro as an approach to predict the behavior of cardiomyocytes facing increased matrix rigidity. Here, we generated pure induced pluripotent stem cell-derived cardiomyocytes and cultured them on engineered polyacrylamide hydrogels matching the elasticities of healthy as well as fibrotic cardiac tissue. Only in cardiomyocytes cultured on matrices with fibrotic-like elasticity, transcriptional profiling revealed a substantial up-regulation of a whole panel of cardiac fibrosis-associated transcripts, including collagen I and III, decorin, lumican, and periostin. In addition, matrix metalloproteinases and their inhibitors, known to be essential in cardiac remodeling, were found to be elevated as well as insulin-like growth factor 2. Control experiments with primary cardiac fibroblasts were analyzed and did not show comparable behavior. In conclusion, we do not only present a snapshot on the transcriptomic fingerprint alterations in cardiomyocytes under pathological conditions but also provide a new reproducible approach to study the effects of fibrotic environments to various cell types.
LB  - PUB:(DE-HGF)16
C6  - pmid:30862552
UR  - <Go to ISI:>//WOS:000466258600015
DO  - DOI:10.1016/j.actbio.2019.03.017
UR  - https://juser.fz-juelich.de/record/861506
ER  -