Uncovering new genes related to heart failure

PhD ceremony: Ms. B. Lu, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Uncovering new genes related to heart failure

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

Faculty: Medical Sciences

Heart failure is characterized by a reduced cardiac output, resulting in decreased exercise capacity, shortness of breath, fatigue and edema. Prognosis for heart failure is poor with a mortality rate of approximately 50% within 5 years. Heart failure is a chronic disease and with the ageing population the incidence of heart failure will increase. Among others, ischemic heart disease, hypertension and valve disease, are the main causes of heart failure development. All these pathologic conditions lead to a series of molecular, cellular and interstitial changes in the heart which are known as cardiac remodeling. Cardiomyocyte hypertrophy (growth) is one of the main remodeling processes and the main topic of this thesis. In this thesis we describe the investigation of gene expression changes that are associated with heart failure development and cardiomyocyte hypertrophy. Heart tissue from healthy rats was compared with those that had developed heart failure. Moreover, expression was analyzed in pure cardiomyocytes cultured in dishes with and without hypertrophic stimulation. This investigation yielded a robust set of hypertrophy/ and heart failure associated genes, including known heart failure genes, but also some which have not previously been linked to heart failure. One identified unknown gene, Dhrs7c, was further investigated. It was shown to be mainly expressed in heart and muscle and importantly its expression was also altered in human heart biopsies from heart failure patients. This confirms that we have generated a dataset that should prove invaluable for a further analysis of human heart failure.