Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cardiac Hypertrophy in a Dish: A Human Stem Cell Based Model

Version 1 : Received: 29 November 2019 / Approved: 30 November 2019 / Online: 30 November 2019 (12:38:21 CET)

How to cite: Johansson, M.; Ulfenborg, B.; X Andersson, C.; Hagvall, S.; Jeppsson, A.; Sartipy, P.; Synnergren, J. Cardiac Hypertrophy in a Dish: A Human Stem Cell Based Model. Preprints 2019, 2019110395. https://doi.org/10.20944/preprints201911.0395.v1 Johansson, M.; Ulfenborg, B.; X Andersson, C.; Hagvall, S.; Jeppsson, A.; Sartipy, P.; Synnergren, J. Cardiac Hypertrophy in a Dish: A Human Stem Cell Based Model. Preprints 2019, 2019110395. https://doi.org/10.20944/preprints201911.0395.v1

Abstract

Cardiac hypertrophy is an important and independent risk factor for the development of heart failure. To better understand the mechanisms and regulatory pathways involved in cardiac hypertrophy, there is a need for improved in vitro models. In this study, we investigated how hypertrophic stimulation affected human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs). The cells were stimulated with endothelin-1 (ET-1) for 8, 24, 48, 72, or 96h. Parameters including cell size, ANP-, proBNP-, and lactate concentration were analyzed. Moreover, transcriptional profiling using RNA-sequencing was performed to identify differentially expressed genes following ET-1 stimulation. The results show that the CMs increase in size by approximately 13% when exposed to ET-1 in parallel to increases in ANP and proBNP protein and mRNA levels. Furthermore, the lactate concentration in the media was significantly increased indicating that the CMs consume more glucose, a hallmark of cardiac hypertrophy. Using RNA-seq, a hypertrophic gene expression pattern was also observed in the stimulated CMs. Taken together, these results show that hiPSC-derived CMs stimulated with ET-1 display a hypertrophic response. The results from this study also provide new molecular insights about the underlying mechanisms of cardiac hypertrophy and may help accelerate the development of new drugs against this condition.

Keywords

cardiac hypertrophy; cardiomyocytes; disease model; endothelin-1; stem cells

Subject

Biology and Life Sciences, Cell and Developmental Biology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.