Cardiomyocytes facing fibrotic conditions re-express extracellular matrix transcripts

Silvia Stotani, Viviana Gatta, Federico Medda, Mohan Padmanaban, Anna Karawajczyk, Päivi Tammela, Fabrizio Giordanetto, Dimitrios Tzalis and Simona Collina

Acta Biomater., Apr. 2019, 89, pp 180-192,  DOI:10.1016/j.actbio.2019.03.017;

Abstract:
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.

Want to know more about this publication?

Contact our scientists

medicinal chemistry

Drug Discovery

We are running our own state-of-the-art Drug Discovery Chemistry facilities in Germany with the option for process research chemistry, upscaling, kilolab production…

performance chemicals

Material Science

We create performance chemicals to enhance new materials, plastics, coatings, dyes & inks, cosmetics, flavors and many more research and industrial applications…

startseite-firstbanner

Looks interesting?

As a leading contract research organization in discovery chemistry and custom synthesis, Taros provides comprehensive solutions to meet our clients’ needs from diverse branches and applications

Our experienced chemists practice a pragmatic culture and customer-centric approach in order to exceed project expectations, despite challenges, bridging very narrow timelines. They are trained to consider economic, safety and ecological boundaries and conditions laid out for all stages of the project, starting from the development of synthetic routes to…