LICAMM The role of matricellular proteins in notch signalling and cell survival after myocardial infarction

Summary

Studies using genetic ablation or activation of Notch signalling have demonstrated that Notch signalling, plays a critical role in cardiac repair and regeneration after myocardial injury. The activation of Notch signalling suppresses cardiomyocytes apoptosis, minimizes fibrosis, increases neovascularization and improves cardiac function and outcome after myocardial infarction (MI). Hence, modulation of Notch signalling may serve as a tool to limit ventricular remodelling and dysfunction after injury. The matricellular protein, tenascin C (TNC) is upregulated following cardiac injury where it plays a role in tissue remodelling. TNC can activate Notch signalling in tumour tissue promoting both survival and growth, however, its role in Notch-mediated cardio-protection in the injured heart remains unexplored. This study aims to investigate the effect of TNC on Notch mediated protective signalling in the heart following injury. Studies will be conducted on isolated cardiac fibroblasts and myoctes as well as mouse models of myocardial injury.

References

1. Natalie Gude, and Mark Sussman. Notch signaling and cardiac repair. J Mol Cell Cardiol. 2012 Jun; 52(6): 1226–1232.
2. Yuxin Li, Yukio Hiroi and James K. Liao. Notch Signaling as an Important Mediator of Cardiac Repair and Regeneration after Myocardial Infarction. Trends Cardiovasc Med. 2010 Oct; 20(7): 228–231.
3. Imanaka-Yoshida K. Tenascin-C in cardiovascular tissue remodeling: from development to inflammation and repair. Circ J. 2012; 76(11):2513-20.
   

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