Cardiomyocytes facing fibrotic conditions re-express extracellular matrix transcripts
Silvia Stotani, Viviana Gatta, Federico Medda, Mohan Padmanaban, Anna Karawajczyk, P盲ivi Tammela, Fabrizio Giordanetto, Dimitrios Tzalis and Simona Collina
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Acta Biomater., Apr. 2019, 89, pp 180-192,听听DOI:10.1016/j.actbio.2019.03.017;
Abstract:
Pathophysiological conditions, such as myocardial infarction and听mechanical overload听affect听the听mammalian听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听in vitro听as an approach to predict the听behavior听of cardiomyocytes facing increased matrix听rigidity. Here, we generated pure induced pluripotent stem cell-derived cardiomyocytes and cultured them on engineered听polyacrylamide听hydrogels听matching the听elasticities听of healthy as well as fibrotic cardiac tissue. Only in cardiomyocytes cultured on matrices with fibrotic-like elasticity, transcriptional profiling revealed a substantial听up-regulation听of a whole panel of cardiac fibrosis-associated transcripts, including听collagen听I and III,听decorin,听lumican, and听periostin. In addition,听matrix metalloproteinases听and their inhibitors, known to be essential in cardiac remodeling, were found to be elevated as well as听insulin-like growth factor 2. Control experiments with primary cardiac听fibroblasts听were analyzed and did not show comparable behavior. In conclusion, we do not only present a snapshot on the听transcriptomic听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.
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