Genetics of human cardiovascular traits

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    Abstract

    This dissertation describes the associations of genetic variants with characteristics of the cardiovascular system, with special interest for blood biomarkers and electrocardiographic traits that reflect cardiac conduction, myocardial mass and myocardial repolarization. The genetic findings have been complemented with in-silico, in-vitro and in-vivo analyses to assess their relevance for cardiovascular biology.

    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 contributionGenetica van cardiovasculaire kenmerken
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • van der Harst, Pim, Supervisor
    • van Gilst, Wiek, Supervisor
    Award date27-May-2015
    Place of Publication[Groningen]
    Publisher
    Print ISBNs9789037778724
    Electronic ISBNs978-90-377-7871-9
    Publication statusPublished - 2015

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