For this conference I got lucky and earned the Travel Award for my poster Mechanosensor YAP1 drives myofibril development and maturation in human cardiomyocytes.
In case you are interested in learning about the work (Introduction, Conclusions) and about our team, read on. In case you want to see the poster contact me (vladimir.vinarsky (at) fnusa.cz) or have a look at the preprint of the work at bioRxiv. Image credit: Zuzana Garlikova
Introduction
Population aging requires new therapies for heart disease
Aging of world population shifts the burden of disease from acute to chronic diseases characterized by loss of fully functional cells. While survival of acute myocardial infarction improved dramatically in last decades, the outlook of cardiac patients diagnosed with heart failure has not improved comparably. New treatment modalities to slow/reverse heart function decline are required.
YAP1 – induced cardiomyocyte proliferation
Repopulation of the failing heart by new cardiomyocytes through reactivation of developmental programs is an active area of research1,2. Mechanosensitive Hippo effector YAP1 is one of the most promising targets. YAP1 promotes proliferation of cardiomyocytes in fetal heart3. Its ectopic expression in adult heart temporarily improves survival after myocardial infarction1,2. However, the newly proliferating cardiomyocytes bring additional challenges. Uncontrolled overgrowth, insufficient maturation, and electrical integration may all outweigh the benefits in the long-term2.
Proliferation independent activity of YAP1
YAP1 is essential for post-mitotic muscle development, required for compensatory hypertrophic response and maintenance of proper calcium homeostasis in vivo4,5. It is therefore possible that milder, yet sufficient effects of more measured increase in YAP1 activity could be leveraged to improve the function of failing heart without cardiomyocyte proliferation.
Aims
Characterize proliferation independent effects of YAP1 activity in human cardiomyocytes on: Cardiac gene expression Cardiomyocyte maturation Morphology of cardiomyocytes and myofibrils Functional properties
Conclusions
- Mechano-transducer YAP1 activates transcription of key cardiac genes with cardiomyocyte maturation fingerprint.
- YAP1 transcriptional activity is required for morphological changes occurring during the in vitro differentiation. These changes can be partially rescued by temporal re-expression of YAP1 in differentiated cardiomyocytes.
- In addition, functional maturation of excitation contraction coupling and calcium metabolism requires YAP1 activity.
Taken together, these new observations of proliferation independent effects of YAP1 activity in human cardiomyocytes offer potential for clinical application.
Research Group
We - the Mechanobiology of Disease Group - are a part of Clinical Research Centre of St. Anne’s Faculty Hospital. Please follow the links to learn more:)