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. 2018;8(3):208-216.
doi: 10.1159/000488949. Epub 2018 May 30.

Determinants of Monocyte Apoptosis in Cardiorenal Syndrome Type 1

Andrea Breglia  1   2   3 , Grazia Maria Virzì  1   2 , Silvia Pastori  1   2 , Alessandra Brocca  1   2   4 , Massimo de Cal  1   2 , Chiara Bolin  5 , Giorgio Vescovo  5   6 , Claudio Ronco  1   2
Affiliations

Determinants of Monocyte Apoptosis in Cardiorenal Syndrome Type 1

Andrea Breglia et al. Cardiorenal Med. 2018.

Abstract

Background: 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.

Material and methods: 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.

Results: 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).

Conclusion: CRS type 1 induces dual apoptotic pathway activation in monocytes; the two pathways converged on caspase-3. Many factors may induce activation of both intrinsic and extrinsic apoptotic pathways in CRS type 1 patients, such as upregulation of proinflammatory cytokines and hypoxia/ischemia. Further investigations are necessary to corroborate the present findings, and to better understand the pathophysiological mechanism and consequent therapeutic and prognostic implications for CRS type 1.

Keywords: Apoptosis; Cardiorenal syndrome; Caspase; Monocytes.

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Figures

Fig. 1.
Fig. 1.
Caspase levels in monocytes exposed to plasma from cardiorenal syndrome (CRS) type 1 and acute heart failure (AHF) patients. The levels of caspase-9 and caspase-8 were significantly higher in monocytes exposed to CRS type 1 compared to AHF.
Fig. 2.
Fig. 2.
Concept figure of apoptosis activation in monocytes exposed to cardiorenal syndrome (CRS) type 1 plasma.
See this image and copyright information in PMC

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