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

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.

Distribution of Cardiac and Renal Corin and Proprotein Convertase Subtilisin/Kexin-6 in the Experimental Model of Cardio-Renal Syndrome of Various Severities

“…As previously reported, rats with ACF exhibited two distinctly different patterns of UnaV. While some of the animals displayed progressive sodium retention, severe dyspnea, and edema, characteristics of decompensated CHF, the remaining rats with ACF, termed compensated subgroup, displayed increased UNaV comparable with those measured in the control group (Khoury et al, 2018). Bodyweight decreased in the compensated (from 343 ± 10 to 328 ± 6 gr) and a more pronounced manner in the decompensated CHF rats (from 339 ± 3 to 294 ± 4 gr).…”

A Genome-Wide Association Study Identifies Five Novel Genetic Markers for Trastuzumab-Induced Cardiotoxicity in Japanese Population

“…25,26) The Notch signaling system is present in the cardiomyocytes and suggested to play a role in myocardial remodeling in heart failure. 27,28) Hence, genetic variation in LINC00558 might contribute to interindividual variability in trastuzumab-induced cardiotoxicity through effects on Notch signaling in the stressed (inactivation of HER2 signaling) cardiomyocyte, although further validation studies will be needed to prove the true association. rs8032978 on chromosome 15q26.3, which is one of the five marker SNPs in this study (P combined = 1.60 × 10 −4 , OR = 5.83, Table 2), was located 44 kb downstream from the PCSK6 gene (Fig.…”

Identification, Localization and Expression of NHE Isoforms in the Alveolar Epithelial Cells

“…Congestive heart failure rat model was induced by surgically creating Aorto -Caval fistula (ACF) as previously described [10]. The abdomens of Sham controls were opened and sutured back again without creating an A -V fistula.…”