Compartmentation of cardiac signalling

Heart failure (HF) represents a major societal and personal burden. Broadly, there are two types of HF: i) HFrEF, with a dilated ventricle and reduced systolic function displaying reduced ejection fraction (EF) and ii) HFpEF, with a stiff heart with concentric hypertrophy, displaying reduced diastolic function and preserved ejection fraction. Treatment for HFrEF includes ACE-inhibitors, angiotensin receptor blockers, SGLT2-inhibitors, spironolactone and β-blockers, whereas effective treatment for HFpEF is so far restricted to certain subgroups of patients.

Our research group is investigating the spatial and temporal signalling through cyclic GMP (cGMP) and cyclic AMP (cAMP) by using FRET-based biosensors localized to specific intracellular compartments in cardiac myocytes. We have a particular emphasis on the role of nitric oxide, natriuretic peptides, beta-adrenergic and 5-HT₄ serotonin receptors with the aim to unravel signalling mechanisms that contribute to improving HFpEF in animal models. To determine if treatment targeting these signalling pathways is effective in HF, we perform both short- and long-term treatment of HFpEF and HFrEF in animal models.