Skip to main content
SpringerLink
Log in

Circulating levels of C1q/TNF-α‐related protein 6 (CTRP6) in coronary artery disease and its correlation with inflammatory markers

  • Research article
  • Published:
Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Introduction

Circulating levels of C1q/TNF-α‐related protein 6 (CTRP6) is an adipokine that is involved in regulation of glucose and lipid metabolism, inflammation, and insulin sensitivity. However, the exact role of CTRP6 in metabolic processes remains unclear due to conflicting findings. To address current gap, we aimed to investigate the serum levels of CTRP6 in patients with coronary artery disease (CAD) and its association with inflammatory cytokines.

Method

In this case-control study, the serum levels of CTRP6, interlukin-6 (IL-6), tumor necrosis factor- α (TNF-α), adiponectin, and fasting insulin were measured using enzyme-linked immunosorbent assay (ELISA) kits in a total of 176 participants, consisting of 88 CAD patients and 88 control subjects. Additionally, various anthropometric and biochemical measurements were measured and compared between cases and controls.

Results

The present study found that serum levels of CTRP6 were significantly higher in the CAD group (561.3 ± 15.14) compared to the control group (429.3 ± 12.85, p < 0.001). After adjusting for age, sex, and body mass index (BMI), CTRP6 levels were found to be positively associated with the risk of CAD (p < 0.001). Correlation analysis in CAD subjects revealed a positive correlation between CTRP6 levels and BMI, systolic blood pressure (SBP), malondialdehyde (MDA), TNF-α, and IL-6, as well as a negative correlation with creatinine and total anti-oxidant capacity.

Conclusion

The findings of this study provide novel evidence that elevated serum levels of CTRP6 are significantly associated with an increased risk of developing CAD. Moreover, our results indicate a correlation between CTRP6 and various risk factors for atherosclerosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

References

  1. Liu L, Shi Z, Ji X, Zhang W, Luan J, Zahr T, et al. Adipokines, adiposity, and atherosclerosis. Cell Mol Life Sci. 2022;79(5):272. https://doi.org/10.1007/s00018-022-04286-2.

    Article  CAS  PubMed  Google Scholar 

  2. Bentzon JF, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formation and rupture. Circ Res. 2014;114(12):1852–66. https://doi.org/10.1161/circresaha.114.302721.

    Article  CAS  PubMed  Google Scholar 

  3. Montarello NJ, Nguyen MT, Wong DTL, Nicholls SJ, Psaltis PJ. Inflammation in coronary atherosclerosis and its therapeutic implications. Cardiovasc Drugs Ther. 2022;36(2):347–62. https://doi.org/10.1007/s10557-020-07106-6.

    Article  CAS  PubMed  Google Scholar 

  4. Bai Y, Sun Q. Macrophage recruitment in obese adipose tissue. Obes Rev. 2015;16(2):127–36. https://doi.org/10.1111/obr.12242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Maddux BA, See W, Lawrence JC Jr., Goldfine AL, Goldfine ID, Evans JL. Protection against oxidative stress-induced insulin resistance in rat L6 muscle cells by mircomolar concentrations of alpha-lipoic acid. Diabetes. 2001;50(2):404–10. https://doi.org/10.2337/diabetes.50.2.404.

    Article  CAS  PubMed  Google Scholar 

  6. Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol. 2004;24(5):816–23. https://doi.org/10.1161/01.Atv.0000122852.22604.78.

    Article  CAS  PubMed  Google Scholar 

  7. Zhou Y, Wei Y, Wang L, Wang X, Du X, Sun Z, et al. Decreased adiponectin and increased inflammation expression in epicardial adipose tissue in coronary artery disease. Cardiovasc Diabetol. 2011;10:2. https://doi.org/10.1186/1475-2840-10-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kawano J, Arora R. The role of adiponectin in obesity, diabetes, and cardiovascular disease. J Cardiometab Syndr. 2009;4(1):44–9. https://doi.org/10.1111/j.1559-4572.2008.00030.x.

    Article  PubMed  Google Scholar 

  9. Zaidi H, Byrkjeland R, Njerve IU, Åkra S, Solheim S, Arnesen H, et al. Adiponectin in relation to exercise and physical performance in patients with type 2 diabetes and coronary artery disease. Adipocyte. 2021;10(1):612–20. https://doi.org/10.1080/21623945.2021.1996699.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fadaei R, Moradi N, Kazemi T, Chamani E, Azdaki N, Moezibady SA, et al. Decreased serum levels of CTRP12/adipolin in patients with coronary artery disease in relation to inflammatory cytokines and insulin resistance. Cytokine. 2019;113:326–31. https://doi.org/10.1016/j.cyto.2018.09.019.

    Article  CAS  PubMed  Google Scholar 

  11. Schäffler A, Buechler C. CTRP family: linking immunity to metabolism. Trends Endocrinol Metab. 2012;23(4):194–204. https://doi.org/10.1016/j.tem.2011.12.003.

    Article  CAS  PubMed  Google Scholar 

  12. Lei X, Seldin MM, Little HC, Choy N, Klonisch T, Wong GW. C1q/TNF-related protein 6 (CTRP6) links obesity to adipose tissue inflammation and insulin resistance. J Biol Chem. 2017;292(36):14836–50. https://doi.org/10.1074/jbc.M116.766808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wang M, Tang X, Li L, Liu D, Liu H, Zheng H, et al. C1q/TNF-related protein-6 is associated with insulin resistance and the development of diabetes in Chinese population. Acta Diabetol. 2018;55(12):1221–9. https://doi.org/10.1007/s00592-018-1203-2.

    Article  CAS  PubMed  Google Scholar 

  14. Zheng WF, Zhang SY, Ma HF, Chang XW, Wang H. C1qTNF-related protein-6 protects against doxorubicin-induced cardiac injury. J Cell Biochem. 2019;120(6):10748–55. https://doi.org/10.1002/jcb.28366.

    Article  CAS  PubMed  Google Scholar 

  15. Murayama MA, Kakuta S, Inoue A, Umeda N, Yonezawa T, Maruhashi T, et al. CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis. Nat Commun. 2015;6(1):1–12.

    Article  Google Scholar 

  16. Kim MJ, Lee W, Park EJ, Park SY. C1qTNF-related protein-6 increases the expression of interleukin-10 in macrophages. Mol Cells. 2010;30(1):59–64. https://doi.org/10.1007/s10059-010-0088-x.

    Article  CAS  PubMed  Google Scholar 

  17. Lei H, Wu D, Wang J-Y, Li L, Zhang C-L, Feng H, et al. C1q/tumor necrosis factor-related protein-6 attenuates post-infarct cardiac fibrosis by targeting RhoA/MRTF-A pathway and inhibiting myofibroblast differentiation. Basic Res Cardiol. 2015;110(4):35. https://doi.org/10.1007/s00395-015-0492-7.

    Article  CAS  PubMed  Google Scholar 

  18. Wei C, Liu Y, Xing E, Ding Z, Tian Y, Zhao Z, et al. Association between Novel Pro- and Anti- Inflammatory adipocytokines in patients with Acute Coronary Syndrome. Clin Appl Thromb Hemost. 2022;28:10760296221128021. https://doi.org/10.1177/10760296221128021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Emamgholipour S, Moradi N, Beigy M, Shabani P, Fadaei R, Poustchi H, et al. The association of circulating levels of complement-C1q TNF-related protein 5 (CTRP5) with nonalcoholic fatty liver disease and type 2 diabetes: a case-control study. Diabetol Metab Syndr. 2015;7:108. https://doi.org/10.1186/s13098-015-0099-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Fadaei R, Moradi N, Baratchian M, Aghajani H, Malek M, Fazaeli AA, et al. Association of C1q/TNF-Related Protein-3 (CTRP3) and CTRP13 serum levels with coronary artery disease in subjects with and without type 2 diabetes Mellitus. PLoS ONE. 2016;11(12):e0168773. https://doi.org/10.1371/journal.pone.0168773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bai B, Ban B, Liu Z, Zhang MM, Tan BK, Chen J. Circulating C1q complement/TNF-related protein (CTRP) 1, CTRP9, CTRP12 and CTRP13 concentrations in type 2 diabetes mellitus: in vivo regulation by glucose. PLoS ONE. 2017;12(2):e0172271.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Seldin MM, Tan SY, Wong GW. Metabolic function of the CTRP family of hormones. Reviews Endocr Metabolic Disorders. 2014;15(2):111–23. https://doi.org/10.1007/s11154-013-9255-7.

    Article  CAS  Google Scholar 

  23. Lu L, Zhang RY, Wang XQ, Liu ZH, Shen Y, Ding FH, et al. C1q/TNF-related protein-1: an adipokine marking and promoting atherosclerosis. Eur Heart J. 2016;37(22):1762–71.

    Article  PubMed  Google Scholar 

  24. Moradi N, Fadaei R, Emamgholipour S, Kazemian E, Panahi G, Vahedi S, et al. Association of circulating CTRP9 with soluble adhesion molecules and inflammatory markers in patients with type 2 diabetes mellitus and coronary artery disease. PLoS ONE. 2018;13(1):e0192159.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wong GW, Krawczyk SA, Kitidis-Mitrokostas C, Revett T, Gimeno R, Lodish HF. Molecular, biochemical and functional characterizations of C1q/TNF family members: adipose-tissue-selective expression patterns, regulation by PPAR-gamma agonist, cysteine-mediated oligomerizations, combinatorial associations and metabolic functions. Biochem J. 2008;416(2):161–77. https://doi.org/10.1042/bj20081240.

    Article  CAS  PubMed  Google Scholar 

  26. Xu E, Yin C, Yi X, Liu Y. Knockdown of CTRP6 inhibits high glucose-induced oxidative stress, inflammation and extracellular matrix accumulation in mesangial cells through regulating the Akt/NF‐κB pathway. Clin Exp Pharmacol Physiol. 2020;47(7):1203–11.

    Article  CAS  PubMed  Google Scholar 

  27. Lee W, Kim MJ, Park EJ, Choi YJ, Park SY. C1qTNF-related protein-6 mediates fatty acid oxidation via the activation of the AMP-activated protein kinase. FEBS Lett. 2010;584(5):968–72. https://doi.org/10.1016/j.febslet.2010.01.040.

    Article  CAS  PubMed  Google Scholar 

  28. Sadeghi A, Fadaei R, Moradi N, Fouani FZ, Roozbehkia M, Zandieh Z et al. Circulating levels of C1q/TNF-α-related protein 6 (CTRP6) in polycystic ovary syndrome. 2020;72(7):1449–59; https://doi.org/10.1002/iub.2272.

  29. Liao X, Liu S, Tang X, Yang D, Liu H, Gao L, et al. Circulating CTRP6 levels are increased in overweight or obese Chinese individuals and Associated with insulin resistance parameters: a pilot study. Experimental and clinical endocrinology & diabetes: official journal. German Soc Endocrinol [and] German Diabetes Association. 2021;129(7):535–41. https://doi.org/10.1055/a-0929-6072.

    Article  CAS  Google Scholar 

  30. Wu WJ, Mo DL, Zhao CZ, Zhao C, Chen YS, Pang WJ, et al. Knockdown of CTRP6 inhibits adipogenesis via lipogenic marker genes and Erk1/2 signalling pathway. Cell Biol Int. 2015;39(5):554–62. https://doi.org/10.1002/cbin.10422.

    Article  CAS  PubMed  Google Scholar 

  31. Wu W, Sun Y, Zhao C, Zhao C, Chen X, Wang G, et al. Lipogenesis in myoblasts and its regulation of CTRP6 by AdipoR1/Erk/PPARγ signaling pathway. Acta Biochim Biophys Sin. 2016;48(6):509–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Li Y, Sun J, Gu L, Gao X. Protective effect of CTRP6 on cerebral ischemia/reperfusion injury by attenuating inflammation, oxidative stress and apoptosis in PC12 cells. Mol Med Rep. 2020;22(1):344–52. https://doi.org/10.3892/mmr.2020.11108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Xu E, Yin C, Yi X, Liu Y. Knockdown of CTRP6 inhibits high glucose-induced oxidative stress, inflammation and extracellular matrix accumulation in mesangial cells through regulating the Akt/NF-κB pathway. Clin Exp Pharmacol Physiol. 2020;47(7):1203–11. https://doi.org/10.1111/1440-1681.13289.

    Article  CAS  PubMed  Google Scholar 

  34. Aronson D, Edelman ER. Coronary artery disease and diabetes mellitus. Cardiol Clin. 2014;32(3):439–55.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Xu J, Zou MH. Molecular insights and therapeutic targets for diabetic endothelial dysfunction. Circulation. 2009;120(13):1266–86. https://doi.org/10.1161/circulationaha.108.835223.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Chi L, Hu X, Zhang W, Bai T, Zhang L, Zeng H, et al. Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats. Biochem Biophys Res Commun. 2017;482(4):727–34. https://doi.org/10.1016/j.bbrc.2016.11.102.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Tehran University of Medical Sciences (TUMS), Tehran, Iran, (grant number: 59099) supported this project. We thank all the patients and individuals participating in the study.

Funding

Tehran University of Medical Sciences (TUMS), Tehran, Iran, (grant number: 59099) supported this project.

Author information

Authors and Affiliations

  1. Department of Cardiology, Dr Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Seyed abdolhossein Tabatabaei, Arash Falahat, Frood malekshahi & Ali Abbasi

  2. Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Reza Fadaei

  3. Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Nariman Moradi

  4. Department of Hematology, Faculty of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Vida Farrokhi

  5. Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

    Akram Vatannejad

  6. Department of Clinical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran

    Reza Afrisham

  7. Department of Pathology, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Mirahmad

Authors
  1. Seyed abdolhossein Tabatabaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Reza Fadaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nariman Moradi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vida Farrokhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akram Vatannejad
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Reza Afrisham
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Arash Falahat
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Frood malekshahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Maryam Mirahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ali Abbasi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Design: Nariman Moradi, Reza Fadaei. Data curation: Ali Abbasi, Seyed abdolhossein Tabatabaei. Formal analysis and Validation: Reza Fadaei. Investigation: Nariman Moradi. Frood Malekshahi, Arash Falahat. Methodology: Nariman Moradi, Akram Vatannejad, Maryam Mirahmad. Project administration: Ali Abbasi, Seyed abdolhosein Tabatabaei. Supervision and Resources: Ali Abbasi. Writing? original draft: Vida Farrokhi, Maryam Mirahmad, Reza Afrisham, Writing? review & editing: Reza Afrisham, Reza Fadaei, Ali Abbasi, Nariman Moradi. Frood Malekshahi, Arash Falahat.

Corresponding author

Correspondence to Ali Abbasi.

Ethics declarations

Ethical approval and consent to participate

This investigation was performed according to the Helsinki Declaration as well as was approved by the Ethics Committee of Tehran University of Medical Sciences (IR.TUMS.SHARIATI.REC.1401.017). All study contributors signed forms of written and informed consent.

Consent for publication

Not applicable.

Competing interests

The authors announce that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tabatabaei, S.a., Fadaei, R., Moradi, N. et al. Circulating levels of C1q/TNF-α‐related protein 6 (CTRP6) in coronary artery disease and its correlation with inflammatory markers. J Diabetes Metab Disord (2024). https://doi.org/10.1007/s40200-024-01415-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s40200-024-01415-5

Keywords

Search

Navigation