PhD ceremony Ms. H. Yu: Exploring AKIP1 function in the heart

PhD ceremony: Ms. H. Yu

Dissertation: Exploring AKIP1 function in the heart

Promotor(s): prof. W.H. van Gilst

Faculty: Medical Sciences

Heart failure (HF) is the common end stage syndrome of many cardiac disorders, which is associated with altered ventricular wall stress triggering cardiac remodeling. Cardiomyocyte growth (hypertrophy), which is often accompanied by energetic reprogramming, is an important process that contributes to cardiac remodeling and HF development. Induction of hypertrophy is accompanied by marked changes in gene expression profiles. The aim of this thesis was to generate an inventory of gene expression changes specific for cardiomyocyte hypertrophy and to further investigate the role of these changes in hypertrophy development . In particular, we explored the function of A kinase interacting protein 1 (AKIP1), which was identified in the inventory as a novel hypertrophy associated gene. We reviewed the current knowledge on gene expression regulation during hypertrophy development. In order to identify novel HF associated genes, we performed a whole genome analysis on several cardiac hypertrophy/HF models and compared the gene expression profiles with their corresponding control groups. Then we investigated the role of AKIP1 in hypertrophy development in NRVCs. Furthermore the effect of AKIP1 on the oxygen consumption rate (OCR) in cardiomyocytes was described. To translate the in vitro findings to the in vivo situation, we generated a cardiac specific AKIP1 transgenic (Tg) mouse line and further investigated the role of AKIP1 in hypertrophy by a TAC mediated pressure overload model.