Public Defence: Tuyet Anh Pham
Cand.med. Tuyet Anh Pham at Institute of Clinical Medicine will be defending the thesis “A study on the cytoprotective actions of CCN2 and the role of CCN2 in angiotensin 2-induced myocardial hypertrophy” for the degree of PhD (Philosophiae Doctor).
Photo: Bettina Nicotra
Trial Lecture – time and place
See Trial Lecture.
- First opponent: Professor Margarete Goppelt-Strübe, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany
- Second opponent: Senior scientist Lise Roman Moltzau, Faculty of Medicine, University of Oslo
- Third member and chair of the evaluation committee: Professor Alessandro Cataliotti, Faculty of Medicine, University of Oslo
Chair of the Defence
Associate Professor Jan Magnus Aronsen, Faculty of Medicine, University of Oslo
Professor Håvard Attramadal, Faculty of Medicine, University of Oslo
CCN2 (or Connective Tissue Growth Factor) is a secreted protein that is almost repressed in normal adult tissue, but is induced in conditions such as myocardial hypertrophy, myocardial infarction, heart failure, and fibrotic disorders.
The aims of the thesis were to decipher CCN2 target cells in the heart and to investigate the functions of CCN2 in ischemia-reperfusion injury and in chronic-pressure overload of the heart.
We demonstrated that CCN2 stimulates adult cardiomyocytes and endothelial cells with activation of the cytoprotective signaling pathway PI3-kinase/Akt/GSK-3β and hence, protection towards hypoxia/reoxygenation induced oxidative stress and cell death. Further, when the cardiomyocytes were stimulated with CCN2 in the presence of the PI3-kinase inhibitor or Akt-inhibitor, we observed that the cardioprotection was attenuated. These findings were supported by the up-regulation of cardioprotective genes in cardiomyocytes stimulated with CCN2.
The antihypertrophic effects of CCN2 were investigated both in vivo and in vitro. Transgenic CCN2 mice with cardiac-restricted overexpression of CCN2 were subjected to angiotensin II-infusion and showed attenuated hypertrophy compared to wild type mice. Similarly, neonatal cardiomyocytes exposed to mechanical stretch in the presence of CCN2 showed reduced NFAT-activity, a recognized pro-hypertrophic signal.
In this work, we have shown that CCN2 activates the cytoprotective signaling pathway PI3-kinase/Akt/GSK-3β in both cardiomyotes and in endothelial cells, and CCN2 increases tolerance towards hypoxia/reoxygenation injury and oxidative stress in cardiomyocytes and endothelial cells, respectively. CCN2 reduces cardiomyocytes hypertrophy induced by angiotensin II and stretch, possibly through modulation of NFAT-activity.
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