Cardiorenal Syndrome Type 1: A Defective Regulation of Monocyte Apoptosis Induced by Proinflammatory and Proapoptotic Factors

Pastori, Silvia; Virzì, Grazia Maria; Brocca, Alessandra; Cal, Massimo de; Clementi, Anna; Vescovo, Giorgio; Ronco, Claudio

doi:10.1159/000371898

Cited by 27 publications

(30 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation of the immune and cellular response, inflammation, oxidative stress, and activation of apoptotic pathways are involved in the pathogenesis of CRS1 [7,9,10,11,12,13]. …”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have specifically shown that apoptosis is implicated in CRS1 pathogenesis [11,12]. These findings suggest the presence of proinflammatory cytokines and proapoptotic factors in CRS1 plasma that induce a defective regulation of monocyte apoptosis in such patients [11,12].…”

Section: Introductionmentioning

confidence: 99%

“…These findings suggest the presence of proinflammatory cytokines and proapoptotic factors in CRS1 plasma that induce a defective regulation of monocyte apoptosis in such patients [11,12]. Unfortunately, the authors of these studies did not elucidate the precise signaling pathway involved in this induced apoptosis: there are two main intracellular pathways for apoptosis (intrinsic and extrinsic) characterized by activation of different activator caspases [22].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cardiorenal Syndrome Type 1: Activation of Dual Apoptotic Pathways

Pastori¹,

Virzì²,

Brocca³

et al. 2015

Cardiorenal Med

Self Cite

View full text Add to dashboard Cite

Cardiorenal syndrome type 1 (CRS1) pathophysiology is complex, and immune-mediated damage, including alterations in the immune response with monocyte apoptosis and cytokine release, has been reported as a potential mechanism. In this study, we examined the putative role of renal tubular epithelial cell (RTC) apoptosis as a pathogenic mechanism in CRS1. In particular, we investigated the caspase pathways involved in induced apoptosis. We enrolled 29 patients with acute heart failure (AHF), 11 patients with CRS1, and 15 controls (CTR) without AHF or acute kidney injury (AKI). Patients who had AKI prior to the episode of AHF or who had any other potential causes of AKI were excluded. Plasma from different groups was incubated with RTCs for 24 h. Subsequently, cell apoptosis, DNA fragmentation, and caspase-3, -8, and -9 activities were investigated in RTCs incubated with AHF, CRS1, and CTR plasma. A p value <0.5 was considered statistically significant. A quantitative analysis of apoptosis showed significantly higher apoptosis rates in CRS1 patients compared to AHF patients and CTR (p < 0.01). This increase in apoptosis was strongly confirmed by caspase-3 levels (ρ = 0.73). Caspase-8 and -9 were significantly higher in CRS1 patients compared to AHF patients and CTR (p < 0.01). Furthermore, caspase-3 levels showed a significantly positive correlation with caspase-8 (ρ = 0.57) and -9 (ρ = 0.47; p < 0.001). This study demonstrated the significantly heightened presence of dual apoptotic disequilibrium in CRS1. Our findings indicated that apoptosis may have a central role in the mechanism of CRS1, and it could be a potential therapeutic target in this syndrome.

show abstract

“…Activation of the immune and cellular response, inflammation, oxidative stress, and activation of apoptotic pathways are involved in the pathogenesis of CRS1 [7,9,10,11,12,13]. …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cardiorenal Syndrome Type 1: Activation of Dual Apoptotic Pathways

Pastori¹,

Virzì²,

Brocca³

et al. 2015

Cardiorenal Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…play an important role in innate and adaptive immune responses to CRS. In particular, experimental data demonstrated that a defective regulation of monocyte apoptosis and an immune-mediated mechanism play a fundamental role in the pathophysiology of type 1 CRS [75]. …”

Section: Can Ecs Function As Antigen-presenting Cells In Crs?mentioning

confidence: 99%

The Role of Dendritic and Endothelial Cells in Cardiorenal Syndrome

et al. 2018

Self Cite

View full text Add to dashboard Cite

Backgrounds: Dendritic cells (DCs) are antigen-presenting cells that play a central role in innate and adaptive immune responses; however, the cross talk between cardiac and renal DCs in cardiorenal syndrome (CRS) has not yet been fully elucidated. In this setting, endothelial cells (ECs) also contribute to immune responses. Summary: DC and EC activation and dysfunction have a central role in the pathogenesis of CRS. Regarding immune responses in CRS, it is unknown whether ECs may serve as antigen-presenting cells or act synergistically with DCs to actively participate in innate and adaptive immune responses. This review first focuses on the burden of concomitant heart and renal DCs in the context of CRS; it examines what is known of DCs in animal models, and proposes a central role for DCs in all types of CRS. Second, this review briefly describes the role of ECs in the context of CRS. Key Messages: Understanding the role of DCs and ECs in immune response could lead to the development of novel therapies for the prevention and treatment of CRS.

show abstract

“…Recently, considerable attention has been paid to the role of new alternative mechanisms, such as epigenetics, prenatal programming, small noncoding RNAs, and extracellular vesicles, which may be part of the pathogenesis of cardiorenal cross-talk [11, 12]. Recent data suggest that both tubular epithelial cells and monocytes, when exposed to plasma of patients with CRS type 1, increase cell apoptosis (DNA fragmentation and augmented caspase activity) and cytokine production (IL-6 and IL-18) [7, 12]. Furthermore, higher levels of reactive oxygen species and reactive nitrogen species production were detected in the plasma of CRS type 1 patients when compared to acute heart failure (AHF) patients [6].…”

Section: Introductionmentioning

confidence: 99%

Determinants of Monocyte Apoptosis in Cardiorenal Syndrome Type 1

Breglia

Pastori

et al. 2018

Cardiorenal Med

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Cardiorenal Syndrome Type 1: A Defective Regulation of Monocyte Apoptosis Induced by Proinflammatory and Proapoptotic Factors

Cited by 27 publications

References 30 publications

Cardiorenal Syndrome Type 1: Activation of Dual Apoptotic Pathways

Cardiorenal Syndrome Type 1: Activation of Dual Apoptotic Pathways

The Role of Dendritic and Endothelial Cells in Cardiorenal Syndrome

Determinants of Monocyte Apoptosis in Cardiorenal Syndrome Type 1

Contact Info

Product

Resources

About