Determinants of Monocyte Apoptosis in Cardiorenal Syndrome Type 1

Autor:	C. Ronco, Giorgio Vescovo, de Cal M, Alessandra Brocca, Chiara Bolin, Andrea Breglia, G M Virzì, Silvia Pastori
Rok vydání:	2018
Předmět:	Male 0301 basic medicine Fas Ligand Protein Urology 030232 urology & nephrology Gene Expression Apoptosis Caspase 3 Cardiorenal syndrome Monocytes Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Bcl-2-associated X protein Humans Medicine Aged bcl-2-Associated X Protein Aged 80 and over Heart Failure Original Paper Caspase 8 Cardio-Renal Syndrome U937 cell biology business.industry Monocyte U937 Cells Middle Aged Fas receptor medicine.disease Caspase 9 Enzyme Activation 030104 developmental biology medicine.anatomical_structure Caspases Cancer research biology.protein Female bcl-Associated Death Protein Cardiology and Cardiovascular Medicine business
Zdroj:	Cardiorenal Medicine. 8:208-216
ISSN:	1664-5502 1664-3828
DOI:	10.1159/000488949
Popis:	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.
Databáze:	OpenAIRE
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