Oncotarget

Research Papers:

Natriuretic peptides system in the pulmonary tissue of rats with heart failure: potential involvement in lung edema and inflammation

Emad E. Khoury, Safa Kinaneh, Doron Aronson, Offer Amir, Diab Ghanim, Natalia Volinsky, Zaher Azzam and Zaid Abassi _

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Oncotarget. 2018; 9:21715-21730. https://doi.org/10.18632/oncotarget.24922

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Abstract

Emad E. Khoury1,*, Safa Kinaneh1,*, Doron Aronson2, Offer Amir3,6, Diab Ghanim3,6, Natalia Volinsky3,6, Zaher Azzam4 and Zaid Abassi1,5

1Department of Physiology, The Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel

2Department of Cardiology, Rambam Health Care Campus, Haifa, Israel

3Department of Cardiology, B Padeh Medical Center, Poriya, Lower Galilee, Israel

4Department of Internal Medicine B, Rambam Health Care Campus, Haifa, Israel

5Department of Laboratory Medicine, Rambam Health Care Campus, Haifa, Israel

6Faculty of Medicine in the Galilee, Bar-Ilan University, Zefat, Israel

*These authors contributed equally to this work

Correspondence to:

Zaid Abassi, email: [email protected]

Keywords: heart failure; lung; corin; PCSK6; natriuretic peptides

Received: December 15, 2017     Accepted: March 05, 2018     Published: April 24, 2018

ABSTRACT

Congestive heart failure (CHF) often leads to progressive cardiac hypertrophy and salt/water retention as evident by peripheral and lung edema. Although the pathogenesis of CHF remains largely unclarified, it is widely accepted that neurohormonal changes and inflammatory processes are profoundly involved in structural and functional deterioration of vital organs including, heart, kidney and lungs. Corin, a cardiac serine protease, is responsible for converting pro-ANP and pro-BNP to biologically active natriuretic peptides (NPs). Although the involvement of corin in cardiac hypertrophy and heart failure was extensively studied, the alterations in corin and PCSK6, a key enzyme in the conversion of procorin to corin, have not been studied in the pulmonary tissue. Thus, this study aims at examining the status of PCSK6/Corin in the lung of rats with CHF induced by the creation of aorto-caval fistula (ACF) between the abdominal aorta and vena cava in SD rats. Rats with ACF were divided into 2 subgroups based on the pattern of their daily sodium excretion, compensated and decompensated CHF. Placement of ACF led to cardiac hypertrophy, pulmonary congestion, and renal dysfunction, which were more severe in the decompensated subgroup, despite remarkable elevation of circulatory ANP and BNP levels. Corin mRNA and immunoreactive peptide were detected in pulmonary tissue of all experimental groups. However, the expression and abundance of pulmonary corin significantly increased in the decompensated animals, but not in the compensated ones. Noteworthy, the expression of PCSK6 and ANP/BNP in the pulmonary tissue followed a similar pattern as corin. The upregulation of pulmonary Corin/PCSK6 and NPs were accompanied by local activation of cathepsin L and certain cytokines including IL-6. In light of the anti-inflammatory role of NPs, we postulate that the obtained upregulation of pulmonary PCSK6/Corin along NPs in rats with decompensated CHF may represent a counterbalance response to the inflammatory milieu characterizing CHF especially in severe cases.


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