Alteration of the Renin–Angiotensin–Aldosterone System in Shock: Role of the Dipeptidyl Peptidase 3

Picod, Adrien; Deniau, Benjamin; Ayar, Prabakar Vaittinada; Genest, Magali; Julian, Nathan; Azibani, Fériel; Mebazaa, Alexandre

doi:10.1164/rccm.202010-3873le

Cited by 15 publications

(12 citation statements)

References 9 publications

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“…In addition to the symptoms of local fracture, severe limb fractures and multiple fractures are usually accompanied by systemic reactions such as massive blood loss and severe pain resulting in traumatic shock which is the main cause of death in fracture patients [ 1 ]. Studies [ 2 , 3 ] have shown that the main cause of death in patients with traumatic shock is the activation of the renin-angiotensin system (RAS) and the upregulation of related cytokine activity, leading to multiple organ damage, among which most commonly kidney damage. Therefore, the goal of improving the prognosis of patients with traumatic shock and reducing their mortality can be achieved by timely and accurate judgment of the patient's condition and taking corresponding measures to alleviate the progress of the condition [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Serum KIM-1, NGAL, and NAG Levels and Correlation with the Diagnostic Value in Patients with Fracture Traumatic Shock

Jiang

Sui

2021

Evidence-Based Complementary and Alternative Medicine

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Traumatic shock is the most common cause of serious adverse outcomes in patients with severe traumatic diseases such as fractures, and some studies here have shown that the main cause of death from traumatic shock is the impairment of organ function that occurs after shock. In this study, we explored the role of serum kidney injury molecule-1 (KIM-1), neutrophil gelatin-related lipid transporter protein (NGAL), and N-acetyl-β-D-glucosidase (NAG) levels in evaluating and diagnosing the condition of patients with fracture traumatic shock based on the goal of contributing to the clinical diagnosis of the patient’s condition as soon as possible and taking measures to alleviate its progress. 96 patients with fracture traumatic shock were included in the study as the observation group and 58 healthy examiners as the control group, and the observation group was divided into 69 cases in the mild-moderate group and 27 cases in the severe group according to the Acute Physiology and Chronic Health Status Scale (APACHE-II). In this study, we detected and analyzed the differences in serum KIM-1, NGAL, and NAG levels between the observation group and the control group and the observation group with different disease levels. We found that the observation group was significantly higher than the control group, and the severe patients were higher than the mild to moderate patients, and we observed that serum KIM-1, NGAL, and NAG are significantly correlated with the condition of patients with fracture traumatic shock after further analysis using the Pearson model. In addition, the diagnostic value of receiver operating characteristic curve analysis showed that the AUC of serum KIM-1 for the diagnosis of fracture traumatic shock was 0.755, the AUC of serum NGAL was 0.750, the AUC of serum NAG was 0.772, and the AUC of the combination of the three indicators was 0.915. The results of this study thus suggest the possibility of serum KIM-1, NGAL, and NAG as clinical indicators for evaluating the condition of patients with fracture traumatic shock and the possibility of a combined test of serum KIM-1, NGAL, and NAG for diagnosing the condition.

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Section: Introductionmentioning

confidence: 99%

Serum KIM-1, NGAL, and NAG Levels and Correlation with the Diagnostic Value in Patients with Fracture Traumatic Shock

Jiang

Sui

2021

Evidence-Based Complementary and Alternative Medicine

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“…This disturbance was initially attributed to decreased ACE activity and AT1R blockade. However, recent reports show that high DPP3 concentrations are found in the blood of critically ill patients, especially the ones suffering from cardiogenic and septic shock [55,95]. The current evidence suggests that enhanced ANG II degradation by DPP3 is an additional explanation for the RAS disturbances observed in shock patients.…”

Section: Involvement In Physiological Functionsmentioning

confidence: 71%

The emerging role of dipeptidyl peptidase 3 in pathophysiology

et al. 2022

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Dipeptidyl peptidase 3 (DPP3), a zinc-dependent aminopeptidase, is a highly conserved enzyme among higher animals. The enzyme cleaves dipeptides from the N-terminus of tetra-to decapeptides, thereby taking part in activation as well as degradation of signalling peptides critical in physiological and pathological processes such as blood pressure regulation, nociception, inflammation and cancer. Besides its catalytic activity, DPP3 moonlights as a regulator of the cellular oxidative stress response pathway, e.g., the Keap1-Nrf2 mediated antioxidative response. The enzyme is also recognized as a key modulator of the renin-angiotensin system. Recently, DPP3 has been attracting growing attention within the scientific community, which has significantly augmented our knowledge of its physiological relevance. Herein, we review recent advances in our understanding of the structure and catalytic activity of DPP3, with a focus on attributing its molecular architecture and catalytic mechanism to its wide-ranging biological functions. We further highlight recent intriguing reports that implicate a broader role for DPP3 as a valuable biomarker in cardiovascular and renal pathologies and furthermore discuss its potential as a promising drug target.International Union of Biochemistry and Molecular Biology system of enzyme nomenclature [1]. Generally,

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“…The primary hypothesis proposed for the imbalance between Ang I and Ang II is a decrease in ACE activity due to endothelial dysfunction [25]. However, the RAS can also be regulated by other peptidases, and one of them is Dipeptidyl-peptidase 3 (DPP3) [36]. DPP3 is a a cytosolic, zinc-dependent metalloprotease expressed ubiquitously in human cells, although its primary function within the intracellular compartment remains unclear [37].…”

Section: Dipeptidyl Peptidase 3: Another Potential Biomarker-guided T...mentioning

confidence: 99%

The role of renin-angiotensin system in sepsis-associated acute kidney injury: mechanisms and therapeutic implications

Garcia,

Zarbock,

Bellomo

et al. 2023

Current Opinion in Critical Care

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Purpose of review This review aims to explore the relationship between the renin angiotensin system (RAS) and sepsis-associated acute kidney injury (SA-AKI), a common complication in critically ill patients associated with mortality, morbidity, and long-term cardiovascular complications. Additionally, this review aims to identify potential therapeutic approaches to intervene with the RAS and prevent the development of AKI. Recent findings Recent studies have provided increasing evidence of RAS alteration during sepsis, with systemic and local RAS disturbance, which can contribute to SA-AKI. Angiotensin II was recently approved for catecholamine resistant vasodilatory shock and has been associated with improved outcomes in selected patients. Summary SA-AKI is a common condition that can involve disturbances in the RAS, particularly the canonical angiotensin-converting enzyme (ACE) angiotensin-II (Ang II)/angiotensin II receptor 1 (AT-1R) axis. Increased renin levels, a key enzyme in the RAS, have been shown to be associated with AKI and may also guide vasopressor therapy in shock. In patients with high renin levels, angiotensin II administration may reduce renin concentration, improve intra-renal hemodynamics, and enhance signaling through the angiotensin II receptor 1. Further studies are needed to explore the role of the RAS in SA-AKI and the potential for targeted therapies.

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Alteration of the Renin–Angiotensin–Aldosterone System in Shock: Role of the Dipeptidyl Peptidase 3

Cited by 15 publications

References 9 publications

Serum KIM-1, NGAL, and NAG Levels and Correlation with the Diagnostic Value in Patients with Fracture Traumatic Shock

Serum KIM-1, NGAL, and NAG Levels and Correlation with the Diagnostic Value in Patients with Fracture Traumatic Shock

The emerging role of dipeptidyl peptidase 3 in pathophysiology

The role of renin-angiotensin system in sepsis-associated acute kidney injury: mechanisms and therapeutic implications

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