Heart failure is currently considered one of the most challenging cardiovascular diseases, with a prevalence of 1-2%. The impact of heart failure is expected to increase substantially with the aging of the population, and despite advances in pharmacological and device treatment of heart failure the prognosis remains very poor. The lack of knowledge surrounding the basis of cardiomyocyte dysfunction and heart failure susceptibility is a major roadblock to understand risk for heart failure and to design innovative strategies for therapy. Innovation in genetic research has been happening at a much faster pace, and is taking the field of biology along. Analyses of the genome wide variation opened up the possibility to study the genetic background of cardiovascular traits in (living) humans and, in turn, study biological mechanisms that may specifically be important for humans, for example in treatment of heart failure. These studies have yielded many new biological insights and pointed to therapeutic targets. For example, we identified genetic variants in the kallikrein-kinin system to be related to biomarkers of cardiac failure that has the potential to serve as a direct therapeutic target.
The genetic findings described in this dissertation provide novel biological insights into cardiac function and could serve as starting point for the development of novel therapeutic interventions. The results will be important for other studies focusing on the molecular mechanisms underlying cardiac function and dysfunction.
|Translated title of the contribution||Genetica van cardiovasculaire kenmerken|
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2015|
Bakker, S. (Creator), Dotinga, A. (Creator), Vonk, J. (Creator), Smidt, N. (Creator), Scholtens, S. (Creator), Swertz, M. (Creator), Wijmenga, C. (Creator), Wolffenbuttel, B. (Creator), Stolk, R. (Creator), van Zon, S. (Creator), Rosmalen, J. (Creator), Postma, D. S. (Creator), de Boer, R. (Creator), Navis, G. (Creator), Slaets, J. (Creator), Ormel, H. (Creator), van Dijk, F. (Creator) & Bolmer, B. (Data Manager), Lifelines, 2006