CyTOheart: Cytohesins in the heart - regulation of natriuretic peptide signaling

Heart failure (HF) is still an increasing problem in the society and we are in need for better HF treatment. This requires better understanding of the mechanisms of myocardial function in normal and failing hearts. In heart failure the heart is no longer able to pump sufficient blood to the body. There are two main subgroups of heart failure. In the first group the heart doesn't contract sufficiently, whereas in the second group the heart doesn't fill with blood sufficiently. The result in both groups is insufficient pumping of blood to the body by the heart. The cardiac hormones natriuretic peptides have the recent years received much attention as potential heart failure therapy. However, the direct effect at the heart is still elusive. Drugs increasing natriuretic peptides have recently been approved for the use in heart failure. Further, drugs that mimic the effect of natriuretic peptides have for several years been suggested in treatment of heart failure. There is still need for more knowledge about beneficial and detrimental effects of natriuretic peptides in the heart. We recently found that natriuretic peptides is involved in the hearts ability to contract. Further, we have results showing that different proteins can regulate the effects of natriuretic peptides in the heart. In this project, we study the role of one of these families of proteins in the regulation of different functional responses of natriuretic peptides in normal and failing hearts. Preliminary results show that this family of proteins is expressed in the heart, affect natriuretic peptid signalling and can potentially affect the response of natriuretic peptides on contraction. This project will increase our knowledge about natriuretic peptides and proteins regulating their responses hopefully contribute to improved treatment of heart failure in the future.

Heart failure (HF) is still an increasing problem in the society and we are in need for better HF treatment. This requires better understanding of the mechanisms of myocardial function in normal and failing hearts. In heart failure the heart is no longer able to pump sufficient blood to the body. There are two main subgroups of heart failure, diastolic/HFpEF (HF with preserved ejection fraction) and systolic/HFrEF (HF with reserved ejection fraction) heart failure. In HFrEF the heart doesn't contract sufficiently, whereas in HFpEF the heart doesn’t fill with blood sufficiently. Both HFrEF and HFpEF results in insufficient pumping of blood to the body by the heart. The cardiac hormones natriuretic peptides have the recent years received much attention as potential heart failure therapy. However, the direct effect at the heart is still elusive. Drugs increasing natriuretic peptides have recently been approved for the use in heart failure. Further, drugs that mimic the effect of natriuretic peptides have for several years been suggested in treatment of heart failure. There is still need for more knowledge about beneficial and detrimental effects of natriuretic peptides in the heart. We recently found that natriuretic peptides is involved in the hearts ability to contract. Further, we have results showing that different proteins can regulate the effects of natriuretic peptides in the heart. In the suggested project, we will study the role of these proteins in the regulation of different functional responses of natriuretic peptides in normal and failing hearts. This project will increase our knowledge about interacting proteins of natriuretic peptide receptors, natriuretic peptides and of the intracellular mechanisms governing heart function and hopefully contribute to new possible targets and improved treatment of heart failure in the future.