Silja Meier‘s research could increase the knowledge of why treatment with natriuretic peptides shows no beneficial long-term effect in heart failure.

MAIN RESULTS:

1. Inhibition of phosphodiesterase 2 enhances the inotropic response in healthy hearts, but not in failing hearts.

2. C-type natriuretic peptide increases cAMP signalling by inhibiting phosphodiesterase 3 in both healthy and failing hearts.

THESIS DEFENCE:

Thesis: Regulation of contractility in non-failing and failing hearts – effects of natriuretic peptides and phosphodiesterases
Candidate: Silja Meier
Time: February 28, 2018 at 13:15
Place: Oslo University Hospital, Rikshospitalet B: Seminar room 2 (B2.U002)
Link to university website (in Norwegian)

SUMMARY:

Overactivity of the cAMP signalling pathway is harmful in heart failure. Meier’s PhD thesis identifies important mechanisms that connect C-type natriuretic peptide (CNP) to increased cAMP activation in both normal and failing hearts.

(1) CNP enhances inotropic and lucitropic responses in both failing and non-failing rat cardiomyocytes by stimulating the NPR-B receptor. The following increase in cGMP is similar in the two groups. The increase leads to reduced activity of the enzyme phosphodiesterase 3 (PDE3) and increased activity of PDE2. Importantly, inhibition of PDE2 amplifies the CNP-induced enhancement of inotropic responses in healthy hearts, but not in failing hearts.

(2) The inhibition of PDE3 activity following CNP stimulation is similar in cardiomyocytes from rats with and without heart failure. Inhibition of PDE3 leads to increased activity of the cAMP signalling pathway and increased cardiomyocyte contractility.

REFERENCES:

(1) Meier, S., Andressen, K. W., Aronsen, J. M., Sjaastad, I., Skomedal, T., Osnes, J. B., Qvigstad, E., Levy, F. O.,  & Moltzau, L. R. (2015, December). Enhancement of cAMP-mediated inotropic responses by CNP is regulated differently by PDE2 in normal and failing hearts. In BMC Pharmacology and Toxicology (Vol. 16, No. S1, p. A66). BioMed Central.

(2) Meier, S., Andressen, K. W., Aronsen, J. M., Sjaastad, I., Hougen, K., Skomedal, T., Osnes, J.-B., Qvigstad, E., Levy, F. O., & Moltzau, L. R. (2017). PDE3 inhibition by C-type natriuretic peptide-induced cGMP enhances cAMP-mediated signaling in both non-failing and failing hearts. European journal of pharmacology, 812, 174-183.