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Metabolic interventions in heart failure

Booij, H., 2017, [Groningen]: Rijksuniversiteit Groningen. 119 p.

Research output: ThesisThesis fully internal (DIV)Academic

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Heart failure (HF) is a major public health problem with a lifetime risk of almost 30% to develop this disease. Despite improved treatment, the mortality rate for HF exceeds that of most malignancies. As one of the most energy-consuming organs in the body, failing energy metabolism is thought to play an important role in the development of HF. In this thesis, we investigated several aspects of metabolic interventions in HF. In the first part we investigated clinical aspects, including the position of β-blockers that have various detrimental effects on metabolism. In a retrospective analysis in low-risk patients with preserved left ventricular ejection fraction after coronary artery bypass grafting (CABG), β-blocker therapy was not associated with reductions in angina or cardiovascular events. These findings suggest that the systematic continuation of β-blockers after CABG is not indicated in these patients. Hypothesis generating studies like these will hopefully help change our approach to the treatment of stable CAD.
In the second part, we aimed to determine whether the A kinase interacting protein 1 (AKIP1) modulates the cardiac response to acute and chronic cardiac stress. Transgenic AKIP1 overexpression does not attenuate cardiac remodeling in response to chronic cardiac stress. AKIP1 does, however, reduce myocardial ischemia / reperfusion injury through stabilization of the mitochondrial permeability transition pore. These findings suggest that AKIP1 deserves further investigation as a putative treatment target for cardioprotection from reperfusion injury during acute myocardial infarction.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
Award date26-Jun-2017
Place of Publication[Groningen]
Publisher
Print ISBNs978-90-367-9794-8
Electronic ISBNs978-90-367-9793-1
Publication statusPublished - 2017

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