Plasma Cold-Inducible RNA-Binding Protein Predicts Lung Dysfunction After Cardiovascular Surgery Following Cardiopulmonary Bypass: A Prospective Observational Study

Xia, Chen; Jiang, Jihong; Wu, Xinping; Li, Jinbao; Li, Shitong

doi:10.12659/msm.914318

Cited by 10 publications

(15 citation statements)

References 29 publications

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“…The elevated levels of CIRP were correlated with the levels of inflammatory cytokines IL‐6 and IL‐10 37 . Furthermore, the length of CPB time was associated with the level of CIRP production, while CIRP level was correlated with the severity of lung dysfunction 37 . In brief, these results suggest that plasma CIRP could serve as a predictor for lung injury after cardiovascular surgery with CPB.…”

Section: Cirp As a Biomarker For Predicting Lung Dysfunction In Patie...mentioning

confidence: 72%

“…The lung is among the most vulnerable organs during the perioperative period of cardiovascular surgery with CPB, and 20% of patients who received cardiovascular surgery had ALI during the perioperative period, with a mortality as high as 80%. Recently, the level of plasma CIRP was demonstrated to be a biomarker for predicting lung dysfunction in patients receiving cardiovascular surgery necessitating CPB 37 . In this study, plasma was collected at different time points during the perioperative period of the cardiovascular surgery with CPB and was then detected for the level of CIRP and inflammatory cytokines, coupled with the collection of other laboratory and clinical parameters at the time 37 .…”

Section: Cirp As a Biomarker For Predicting Lung Dysfunction In Patie...mentioning

confidence: 99%

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The role of Cold‐Inducible RNA‐binding protein in respiratory diseases

Zhong

Zhou

Zhang

et al. 2021

J Cellular Molecular Medi

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Cold‐inducible RNA‐binding protein (CIRP) is a stress‐response protein that is expressed in various types of cells and acts as an RNA chaperone, modifying the stability of its targeted mRNA. Intracellular CIRP could also be released into extracellular space and once released, extracellular CIRP (eCIRP) acts as a damage‐associated molecular pattern (DAMP) to induce and amplify inflammation. Recent studies have found that eCIRP could promote acute lung injury (ALI) via activation of macrophages, neutrophils, pneumocytes and lung vascular endothelial cells in context of sepsis, haemorrhagic shock, intestinal ischemia/reperfusion injury and severe acute pancreatitis. In addition, CIRP is also highly expressed in the bronchial epithelial cells and its expression is upregulated in the bronchial epithelial cells of patients with chronic obstructive pulmonary diseases (COPD) and rat models with chronic bronchitis. CIRP is a key contributing factor in the cold‐induced exacerbation of COPD by promoting the expression of inflammatory genes and hypersecretion of airway mucus in the bronchial epithelial cells. Besides, CIRP is also involved in regulating pulmonary fibrosis, as eCIRP could directly activate and induce an inflammatory phenotype in pulmonary fibroblast. This review summarizes the findings of CIRP investigation in respiratory diseases and the underlying molecular mechanisms.

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Section: Cirp As a Biomarker For Predicting Lung Dysfunction In Patie...mentioning

confidence: 72%

Section: Cirp As a Biomarker For Predicting Lung Dysfunction In Patie...mentioning

confidence: 99%

The role of Cold‐Inducible RNA‐binding protein in respiratory diseases

Zhong

Zhou

Zhang

et al. 2021

J Cellular Molecular Medi

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“…Cen et al 28 demonstrated that CIRP deficiency can attenuate inflammation and oxidative stress and reduce renal injury after renal ischemia-reperfusion. Chen et al 29 found that the expression of CIRP in serum increased rapidly after CPB, then decreased gradually, and approached the preoperative level at 5 days after CPB. CIRP level could serve as a biomarker to predict the lung injury induced by cardiovascular surgery.…”

Section: Discussionmentioning

confidence: 98%

CIRP Secretion during Cardiopulmonary Bypass Is Associated with Increased Risk of Postoperative Acute Kidney Injury

Liu

Yang

Han

et al. 2021

Thorac Cardiovasc Surg

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Background Systemic inflammation contributes to cardiac surgery–associated acute kidney injury (AKI). Cardiomyocytes and other organs experience hypothermia and hypoxia during cardiopulmonary bypass (CPB), which induces the secretion of cold-inducible RNA-binding protein (CIRP). Extracellular CIRP may induce a proinflammatory response. Materials and Methods The serum CIRP levels in 76 patients before and after cardiac surgery were determined to analyze the correlation between CIRP levels and CPB time. The risk factors for AKI after cardiac surgery and the in-hospital outcomes were also analyzed. Results The difference in the levels of CIRP (ΔCIRP) after and before surgery in patients who experienced cardioplegic arrest (CA) was 26-fold higher than those who did not, and 2.7-fold of those who experienced CPB without CA. The ΔCIRP levels were positively correlated with CPB time (r = 0.574, p < 0.001) and cross-clamp time (r = 0.54, p < 0.001). Multivariable analysis indicated that ΔCIRP (odds ratio: 1.003; 95% confidence interval: 1.000–1.006; p = 0.027) was an independent risk factor for postoperative AKI. Patients who underwent aortic dissection surgery had higher levels of CIRP and higher incidence of AKI than other patients. The incidence of AKI and duration of mechanical ventilation in patients whose serum CIRP levels more than 405 pg/mL were significantly higher than those less than 405 pg/mL (65.8 vs. 42.1%, p = 0.038; 23.1 ± 18.2 vs. 13.8 ± 9.2 hours, p = 0.007). Conclusion A large amount of CIRP was released during cardiac surgery. The secreted CIRP was associated with the increased risk of AKI after cardiac surgery.

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“…[21,22] In adult human patients, elevated plasma levels of eCIRP have been correlated with a poor prognosis in patients with sepsis and with lung dysfunction after cardiac surgery. [19,23,24] However, to our knowledge, eCIRP levels have never been assessed in neonates. Furthermore, the impact of eCIRP on cardiac tissue or cardiac function has never been studied.…”

Section: Introductionmentioning

confidence: 99%

Targeting the eCIRP/TREM-1 Interaction with a Small Molecule Inhibitor Improves Cardiac Dysfunction in Neonatal Sepsis

Denning

Aziz

et al. 2020

Preprint

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Background: Neonatal sepsis and the associated myocardial dysfunction remain a leading cause of infant mortality. Extracellular cold-inducible RNA-binding protein (eCIRP) acts as a ligand of triggering receptor expressed on myeloid cells-1 (TREM-1). M3 is a small CIRP-derived peptide that inhibits the eCIRP/TREM-1 interaction. We hypothesize that the eCIRP/TREM-1 interaction in cardiomyocytes contributes to sepsis-induced cardiac dysfunction in neonatal sepsis, while M3 is cardioprotective. Methods: Serum was collected from neonates in the Neonatal Intensive Care Unit (NICU). 5-7-day old C57BL/6 mouse pups were used in this study. Primary murine neonatal cardiomyocytes were stimulated with recombinant murine (rm) CIRP with M3. TREM-1 mRNA and supernatant cytokine levels were assayed. Mitochondrial oxidative stress, ROS, and membrane potential were assayed. Neonatal mice were injected with rmCIRP and speckle-tracking echocardiography was conducted to measure cardiac strain. Sepsis was induced by i.p. cecal slurry. Mouse pups were treated with M3 or vehicle. After 16 h, echocardiography was performed followed by euthanasia for tissue analysis. A 7-day survival study was conducted. Results: Serum CIRP levels were elevated in septic human neonates. rmCIRP stimulation of cardiomyocytes increased TREM-1 gene expression. Stimulation of cardiomyocytes with rmCIRP upregulated TNF-α and IL-6 in the supernatants, while this upregulation was inhibited by M3. Stimulation of cardiomyocytes with rmCIRP resulted in a reduction in mitochondrial membrane potential (MMP) while M3 treatment returned MMP to near baseline. rmCIRP caused mitochondrial calcium overload; this was inhibited by M3. rmCIRP injection impaired longitudinal and radial cardiac strain. Sepsis resulted in cardiac dysfunction with a reduction in cardiac output and left ventricular end diastolic diameter. Both were improved by M3 treatment. Treatment with M3 attenuated serum, cardiac, and pulmonary levels of pro-inflammatory cytokines compared to vehicle-treated septic neonates. M3 dramatically increased sepsis survival. Conclusions: Inhibition of eCIRP/TREM-1 interaction with M3 is cardioprotective, decreases inflammation, and improves survival in neonatal sepsis. Trial registration: Retrospectively registered.

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Plasma Cold-Inducible RNA-Binding Protein Predicts Lung Dysfunction After Cardiovascular Surgery Following Cardiopulmonary Bypass: A Prospective Observational Study

Cited by 10 publications

References 29 publications

The role of Cold‐Inducible RNA‐binding protein in respiratory diseases

The role of Cold‐Inducible RNA‐binding protein in respiratory diseases

CIRP Secretion during Cardiopulmonary Bypass Is Associated with Increased Risk of Postoperative Acute Kidney Injury

Targeting the eCIRP/TREM-1 Interaction with a Small Molecule Inhibitor Improves Cardiac Dysfunction in Neonatal Sepsis

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