Novel heart failure biomarkers: Physiological studies to understand their complexityDu, W., 2019, [Groningen]: University of Groningen. 181 p.
Research output: Thesis › Thesis fully internal (DIV) › Academic
The emerging novel heart failure (HF) biomarkers have been shown to provide additional value for prognosis and disease management. However, their plasma levels can be affected by other diseases and potential HF co-morbidities. This may explain why these purported HF biomarkers have still not found their way into daily clinical practice, in contrast to natriuretic peptides. Additionally, these biomarkers may also constitute interesting therapeutic targets. Therefore, we explore the potential of therapeutic targeting of certain HF biomarkers and investigate the cardiac and non-cardiac contribution of HF biomarkers in cardiac disease by using mouse and rat HF models. We demonstrated mechanistic insights of miR-328 in promoting cardiac fibrosis and the potentials as a therapeutic target for treatment of cardiac fibrotic disease by a specific antagomir. Pharmacological inhibition of myeloperoxidase (MPO), only temporally delayed but did not inhibit cardiac remodeling upon pressure overload. The absence of MPO elevation post-TAC is opposite to what has been found in post-MI mouse studies, indicating the role of MPO in cardiac remodeling may be dependent on the etiology. Our comprehensive HF animal models in mouse and in rat revealed that only ANP plasma levels can indicated specific indices for cardiac remodeling, but other alleged novel biomarkers (Gal-3, GDF-15 and TIMP1) may also reflect stress in other organs, either as a consequence of the failing heart and/or as a consequence of other underlying comorbidities. More studies are needed to better understand organ plasma biomarker contribution under different disease states for providing better explanation of their biology.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2019|
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