Cardiomyocyte proliferation prevents failure in pressure overload but not volume overload
2017 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Cardiomyocyte proliferation prevents failure in pressure overload but not volume overload
Toischer, K. ; Zhu, W.; Hünlich, M.; Mohamed, B. A.; Khadjeh, S.; Reuter, S. P. & Schäfer, K. et al. (2017)
Journal of Clinical Investigation, 127(12) pp. 4285-4296. DOI: https://doi.org/10.1172/JCI81870
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- Authors
- Toischer, Karl ; Zhu, Wuqiang; Hünlich, Mark; Mohamed, Belal A.; Khadjeh, Sara; Reuter, Sean P.; Schäfer, Katrin ; Ramanujam, Deepak; Engelhardt, Stefan; Hasenfuß, Gerd
- Abstract
- Induction of the cell cycle is emerging as an intervention to treat heart failure. Here, we tested the hypothesis that enhanced cardiomyocyte renewal in transgenic mice expressing cyclin D2 would be beneficial during hemodynamic overload. We induced pressure overload by transthoracic aortic constriction (TAC) or volume overload by aortocaval shunt in cyclin D2–expressing and WT mice. Although cyclin D2 expression dramatically improved survival following TAC, it did not confer a survival advantage to mice following aortocaval shunt. Cardiac function decreased following TAC in WT mice, but was preserved in cyclin D2–expressing mice. On the other hand, cardiac structure and function were compromised in response to aortocaval shunt in both WT and cyclin D2–expressing mice. The preserved function and improved survival in cyclin D2–expressing mice after TAC was associated with an approximately 50% increase in cardiomyocyte number and exaggerated cardiac hypertrophy, as indicated by increased septum thickness. Aortocaval shunt did not further impact cardiomyocyte number in mice expressing cyclin D2. Following TAC, cyclin D2 expression attenuated cardiomyocyte hypertrophy, reduced cardiomyocyte apoptosis, fibrosis, calcium/calmodulin–dependent protein kinase IIδ phosphorylation, brain natriuretic peptide expression, and sustained capillarization. Thus, we show that cyclin D2–induced cardiomyocyte renewal reduced myocardial remodeling and dysfunction after pressure overload but not after volume overload.
- Issue Date
- 2017
- Journal
- Journal of Clinical Investigation
- Project
- SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz
SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur
SFB 1002 | D04: Bedeutung der Methylierung von RNA (m6A) und des Histons H3 (H3K4) in der Herzinsuffizienz
SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle - Working Group
- RG Hasenfuß (Transition zur Herzinsuffizienz)
RG Schäfer (Translationale Vaskuläre Biologie)
RG Toischer (Kardiales Remodeling) - ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English