Determinants of Monocyte Apoptosis in Cardiorenal Syndrome Type 1

Cardiorenal Medicine
Andrea BregliaClaudio Ronco

Abstract

Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Its pathophysiology is complex and not completely understood. In this study, we examined the role of apoptosis and the caspase pathways involved. We enrolled 40 acute heart failure (AHF) patients, 11 of whom developed AKI characterizing CRS type 1. We exposed the human cell line U937 to plasma from the CRS type 1 and AHF groups and then we evaluated apoptotic activity by annexin-V evaluation, determination of caspase-3, -8 and -9 levels, and BAX, BAD, and FAS gene expression. We observed significant upregulation of apoptosis in monocytes exposed to CRS type 1 plasma compared to AHF, with increased levels of caspase-3 (p < 0.01), caspase-9 (p < 0.01), and caspase-8 (p < 0.03) showing activation of both intrinsic and extrinsic pathways. Furthermore, monocytes exposed to CRS type 1 plasma had increased gene expression of BAX and BAD (intrinsic pathways) (p = 0.010 for both). Furthermore, strong significant correlations between the caspase-9 levels and BAD and BAX gene expression were observed (Spearman ρ = - 0.76, p = 0.011, and ρ = - 0.72, p = 0.011). CRS type 1 induces dual apoptotic pathway ac...Continue Reading

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Citations

Nov 30, 2019·Lancet·Claudio RoncoJohn A Kellum
Jul 1, 2020·Current Vascular Pharmacology·Evangelia DounousiCarmine Zoccali
Aug 8, 2021·Cells·Beatriz Delgado-ValeroErnesto Martínez-Martínez
Apr 3, 2019·Cardiorenal Medicine·Grazia Maria VirzìClaudio Ronco

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