Research Article
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Predictive value of NLRC3 levels for pulmonary hypertension in patients with chronic obstructive pulmonary disease

Year 2024, Volume: 10 Issue: 3, 262 - 267, 04.05.2024
https://doi.org/10.18621/eurj.1357708

Abstract

Objectives: Chronic obstructive pulmonary disease (COPD) is a medical condition defined by persistent airflow limitation and respiratory symptoms caused by airway and/or alveolar abnormalities. Pulmonary hypertension (PH) is one of the cardiovascular comorbidities associated with COPD. We investigated the correlation of NLRC3 levels in patients with COPD with prognostic and surrogate parameters of PH on echocardiography and examined whether it could be used to predict PH in this patient population.

Methods: A total of 80 patients diagnosed with COPD and 40 healthy volunteers as the control group were included in the study. The COPD group was further divided into two subgroups according to the systolic pulmonary artery pressure (sPAP) as follows: sPAP<35 mmHg and sPAP≥35 mmHg. The enzyme-linked immunosorbent assay (ELISA) method was used to determine the levels of NLRC3 in peripheral blood.

Results: Patients with sPAP≥35 mmHg had a lower mean NLRC3 level than those with sPAP<35 mmHg (P=0.006). The NLRC3 levels showed a significant negative correlation with sPAP, tricuspid regurgitation velocity, right atrium, and pulmonary artery diameter. For NLRC3, the cut-off value was found to be 271,486 ng/L, with a sensitivity of 74%, and specificity of 63% in distinguishing patients with sPAP≥35 mmHg from all patients with sPAP<35 mmHg.

Conclusions: Our study results suggest that NLRC3 levels measured from peripheral blood are predictive of PH in patients with COPD. Although the exact function of NLRC3 in the lungs, COPD, and PH have not been completely understood, we believe these findings will serve as a model for future studies.

Ethical Statement

The study protocol was approved by the the Tekirdağ Namık Kemal University, Non-Interventional Clinical Research Ethics Committee (No: 2019.164.09.24, date: 24/09/2019).

Supporting Institution

Tekirdağ Namık Kemal University (project number: NKUBAP.02.TU.20.249).

Project Number

NKUBAP.02.TU.20.249

References

  • 1. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023. Available from: https://goldcopd.org/2023-gold-report-2/ Accessed on September 1, 2023.
  • 2. Jyothula S, Safdar Z. Update on pulmonary hypertension complicating chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2009;4:351-63. doi: 10.2147/copd.s5102.
  • 3. Seeger W, Adir Y, Barberà JA, et al. Pulmonary hypertension in chronic lung diseases. J Am Coll Cardiol. 2013;62(25 Suppl):D109-116. doi: 10.1016/j.jacc.2013.10.036.
  • 4. Davis BK, Wen H, Ting JP. The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu Rev Immunol. 2011;29:707-735. doi: 10.1146/annurev-immunol-031210-101405.
  • 5. Chen G, Shaw MH, Kim YG, Nuñez G. NOD-like receptors: role in innate immunity and inflammatory disease. Annu Rev Pathol. 2009;4:365-398. doi: 10.1146/annurev.pathol.4.110807.092239.
  • 6. Karki R, Man SM, Malireddi RKS, et al. NLRC3 is an inhibitory sensor of PI3K-mTOR pathways in cancer. Nature. 2016;540(7634):583-587. doi: 10.1038/nature20597.
  • 7. Zha LH, Zhou J, Li TZ, et al. NLRC3: a novel noninvasive biomarker for pulmonary hypertension diagnosis. Aging Dis. 2018;9(5):843-851. doi: 10.14336/AD.2017.1102.
  • 8. Chaouat A, Naeije R, Weitzenblum E. Pulmonary hypertension in COPD. Eur Respir J. 2008;32(5):1371-1385. doi: 10.1183/09031936.00015608.
  • 9. Chaput C, Sander LE, Suttorp N, Opitz B. NOD-like receptors in lung siseases. Front Immunol. 2013;4:393. doi: 10.3389/fimmu.2013.00393.
  • 10. Schneider M, Zimmermann AG, Roberts RA, et al. The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription factor NF-κB. Nat Immunol. 2012;13(9):823-831. doi: 10.1038/ni.2378.
  • 11. Ghio S, Klersy C, Magrini G, et al. Prognostic relevance of the echocardiographic assessment of right ventricular function in patients with idiopathic pulmonary arterial hypertension. Int J Cardiol. 2010;140(3):272-278. doi: 10.1016/j.ijcard.2008.11.051.
  • 12. Zha LH, Zhou J, Li TZ, et al. NLRC3 inhibits MCT-induced pulmonary hypertension in rats via attenuating PI3K activation. J Cell Physiol. 2019;234(9):15963-15976. doi: 10.1002/jcp.28255.
Year 2024, Volume: 10 Issue: 3, 262 - 267, 04.05.2024
https://doi.org/10.18621/eurj.1357708

Abstract

Project Number

NKUBAP.02.TU.20.249

References

  • 1. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023. Available from: https://goldcopd.org/2023-gold-report-2/ Accessed on September 1, 2023.
  • 2. Jyothula S, Safdar Z. Update on pulmonary hypertension complicating chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2009;4:351-63. doi: 10.2147/copd.s5102.
  • 3. Seeger W, Adir Y, Barberà JA, et al. Pulmonary hypertension in chronic lung diseases. J Am Coll Cardiol. 2013;62(25 Suppl):D109-116. doi: 10.1016/j.jacc.2013.10.036.
  • 4. Davis BK, Wen H, Ting JP. The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu Rev Immunol. 2011;29:707-735. doi: 10.1146/annurev-immunol-031210-101405.
  • 5. Chen G, Shaw MH, Kim YG, Nuñez G. NOD-like receptors: role in innate immunity and inflammatory disease. Annu Rev Pathol. 2009;4:365-398. doi: 10.1146/annurev.pathol.4.110807.092239.
  • 6. Karki R, Man SM, Malireddi RKS, et al. NLRC3 is an inhibitory sensor of PI3K-mTOR pathways in cancer. Nature. 2016;540(7634):583-587. doi: 10.1038/nature20597.
  • 7. Zha LH, Zhou J, Li TZ, et al. NLRC3: a novel noninvasive biomarker for pulmonary hypertension diagnosis. Aging Dis. 2018;9(5):843-851. doi: 10.14336/AD.2017.1102.
  • 8. Chaouat A, Naeije R, Weitzenblum E. Pulmonary hypertension in COPD. Eur Respir J. 2008;32(5):1371-1385. doi: 10.1183/09031936.00015608.
  • 9. Chaput C, Sander LE, Suttorp N, Opitz B. NOD-like receptors in lung siseases. Front Immunol. 2013;4:393. doi: 10.3389/fimmu.2013.00393.
  • 10. Schneider M, Zimmermann AG, Roberts RA, et al. The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription factor NF-κB. Nat Immunol. 2012;13(9):823-831. doi: 10.1038/ni.2378.
  • 11. Ghio S, Klersy C, Magrini G, et al. Prognostic relevance of the echocardiographic assessment of right ventricular function in patients with idiopathic pulmonary arterial hypertension. Int J Cardiol. 2010;140(3):272-278. doi: 10.1016/j.ijcard.2008.11.051.
  • 12. Zha LH, Zhou J, Li TZ, et al. NLRC3 inhibits MCT-induced pulmonary hypertension in rats via attenuating PI3K activation. J Cell Physiol. 2019;234(9):15963-15976. doi: 10.1002/jcp.28255.
There are 12 citations in total.

Details

Primary Language English
Subjects Chest Diseases
Journal Section Original Articles
Authors

Meltem Yılmaz 0000-0003-0314-4774

Levent Cem Mutlu 0000-0002-3535-5704

Şeref Alpsoy 0000-0003-3720-0076

Aydın Akyüz 0000-0003-3304-4125

Aliye Çelikkol 0000-0002-3799-4470

Özlem Kaymaz 0000-0001-5710-3316

Project Number NKUBAP.02.TU.20.249
Early Pub Date December 28, 2023
Publication Date May 4, 2024
Submission Date September 11, 2023
Acceptance Date December 21, 2023
Published in Issue Year 2024 Volume: 10 Issue: 3

Cite

AMA Yılmaz M, Mutlu LC, Alpsoy Ş, Akyüz A, Çelikkol A, Kaymaz Ö. Predictive value of NLRC3 levels for pulmonary hypertension in patients with chronic obstructive pulmonary disease. Eur Res J. May 2024;10(3):262-267. doi:10.18621/eurj.1357708

e-ISSN: 2149-3189 


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