1. Neprilysin and natriuretic peptide receptor C – new, interesting targets for heart failure therapy
No conflicts of interest decleared
K. Kodziszewska1, P. Leszek1, B. Sochanowicz, K. Brzoska2, M. Pronicki3, T. Zieliński2
1Department of Heart Failure and Transplantology, Institute of Cardiology, Warsaw, Poland
2Institute of Nuclear Chemistry and Technology, Centre for Radiobiology and Biological Dosimetry, Warsaw, Poland
3Department of Pathology, Children’s Memorial Health Institute, Warsaw, Poland

2. Natriuretic peptide clearance system
Type natriuretic peptide receptor C
Binds all natriuretic peptides (NP) with similar affinity
Eliminates NPs from the system by internalization/lyzosomal degradation
Upon stimulation with ANP and/or CNP produces biological effect via adenylyl cyclase and PLC pathways
Neutral endopeptidase
Membrane-bound and soluble forms
Distributed in a variety of tissues
Breaks down a variety of substances, bradykinin, angiotensin -1,-2,-3, endothelin -1,-2, and -3
Breaks down NPs in the order of affinity CNP=ANP>BNP

3. Study material
Study group – cardiac tissue obtained from 43 patients subject to heart transplantation due to advanced heart failure
Control group – hearts obtained from 12 healthy organ donors not allocated to transplantation due to technical reasons

4. Type C natriuretic peptide receptor
mRNA (PCR)
Protein - ELISA p=
p=0.0014
Relative expression of NPR-C receptor in a non-failing vs. failing heart

5. Cardiac expression and function of neutral endopeptidase
Protein - ELISA
Function - FLUORIMETRY
p<
p=0.4181
Neutral endopeptidase expression and activity in non-failing vs. failing hearts

6. Conclusions
Heart failure is associated with augmented NPR-C expression on mRNA level
However, on a protein level NPR-C expression is reduced
Neutral endopeptidase levels remain unchanged in failing vs. non-failing hearts, while its activity significantly increases in heart failure – a finding that strongly supports the rationale behind clinical application of NEP inhibitors