Diagnostic and therapeutic potential of microRNA-212 in HFpEF.

Heart failure is the cardiovascular epidemic of the 21st century, due to population ageing and improved cardiovascular therapy. Half of heart failure patients has a preserved ejection fraction, but little is known about these 'HFpEF' patients. HFpEF pathophysiology is incompletely understood, and no existing treatment is able to improve prognosis (50% mortality at 5 years). A complicating factor is the heterogeneity of HFpEF patients: different phenotypes seem to exist, but in large clinical trials these are all classified under one 'HFpEF' category.MicroRNA seem to play an important role in HFpEF pathophysiology. MicroRNA are epigenetic regulators controlling countless biological processes and are stable in the circulation, which makes them attractive biomarkers. Also, microRNA-based therapy is easy to administer and expected effects are large, due to numerous downstream targets. We recently discovered that microRNA-212 is linked to the response to exercise training in HFpEF patients. Additionally, we found increased microRNA-212 in hearts of an ageing mouse model of HFpEF.In this project, we want to establish the diagnostic and therapeutic potential of microRNA-212 in HFpEF. Our translational approach guarantees relevant results: on one hand, we use several animal models of HFpEF (representing different clinical phenotypes) to test microRNA-212 in a therapeutic setting, on the other hand we set up a longitudinal clinical study to check the diagnostic potential of microRNA-212 with regards to the different HFpEF phenotypes.This study will evaluate microRNA-212 as a possible biomarker and therapeutic target in HFpEF. The translational design will facilitate future clinical trials. Finally, this project will gather much-needed insight in the pathophysiology of HFpEF.

Keywords:EPIGENETICS, EXERCISE PHYSIOLOGY, HEART FAILURE

Disciplines:Cardiac and vascular medicine, Physiology