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Higher circulating levels of ANGPTL8 are associated with body mass index, triglycerides, and endothelial dysfunction in patients with coronary artery disease

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Abstract

Bac Coronary artery disease (CAD) is the leading cause of death worldwide and most commonly develops as a result of atherosclerosis. ANGPTL8 is a secreted adipokine that regulates lipid metabolism and is associated with cardiometabolic diseases, including type 2 diabetes and CAD. However, the association between circulating ANGPTL8 levels and CAD is inconsistent among studies and the mechanism by which ANGPTL8 contributes to CAD development remains poorly understood. Here we sought to evaluate the relationship between ANGPTL8 levels and endothelial dysfunction and adipose tissue inflammation in CAD patients. Concentrations of ANGPTL8, adiponectin, TNF-α, IL6, hsCRP, ICAM-1, and VCAM-1 were measured by ELISA in serum samples from 192 CAD patients diagnosed with stenosis > 50% in at least one coronary artery by angiography and 71 individuals with normal heart function. Serum ANGPTL8 levels were significantly higher in CAD patients compared to controls (83.84 ± 23.25 ng/mL vs. 50.45 ± 17.73; p < 0.001), independent of adjustment for age, sex, BMI, smoking and statin use. ANGPTL8 could also differentiate CAD patients from controls with 82.3% specificity and 81.4% sensitivity (p < 0.001). Adiponectin levels were lower in CAD patients, while ICAM-1, VCAM-1, TNF-α, IL6, and hsCRP levels were higher compared to non-CAD controls (all p < 0.001). ANGPTL8 levels were associated with BMI in controls and with BMI, TG, and ICAM-1 in CAD patients. The presence of elevated ANGPTL8 levels in CAD patients and independent association with TG and ICAM-1 suggest a possible role related to endothelial dysfunction in the pathogenesis of atherosclerosis.

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Data availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors wish to thank Brandon S. Davies, PhD from Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa Carver College of Medicine, Iowa City for helpful feedback and comments in preparation of the manuscript.

Funding

The study was funded by Molecular Medicine Research Center, Hamadan University of Medical Sciences (No. 9609075609).

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Author notes

  1. Reza Fadaei and Hossein Shateri have contributed equally to this work.

Authors and Affiliations

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

    Reza Fadaei

  2. Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Hossein Shateri, Mohammad Mohammadi & Nasrin Ziamajidi

  3. Diabetes and Fibrotic Disease Unit, Translational Genomics Research Institute, 445 N 5th Street, Phoenix, AZ, 85004, USA

    Johanna K. DiStefano

  4. Department of Clinical Biochemistry, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Nariman Moradi

  5. Department of Cardiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Nariman Moradi & Farzad Emami

  6. Interventional Cardiology Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran

    Hassan Aghajani

  7. Molecular Medicine Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Nasrin Ziamajidi

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  1. Reza Fadaei
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Contributions

R.F., H.S., and N.Z. generated and developed the study hypothesis and design. R.F., H.S., N.M., F.E., and H.A. collected the data. R.F. analyzed and interpreted the data. R.F., H.S., J.K.D., N.M., M.M., F.E., H.A., and N.Z. drafted and revised the manuscript. R.F., J.K.D., M.M., and N.Z. completed the final version of manuscript. All authors read and confirmed the final manuscript.

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Correspondence to Nasrin Ziamajidi.

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The study approved by the Ethics committee of Hamadan University of Medical Sciences (IR.UMSHA.REC.1396.535) and was conducted in accordance with the Declaration of Helsinki.

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Fadaei, R., Shateri, H., DiStefano, J.K. et al. Higher circulating levels of ANGPTL8 are associated with body mass index, triglycerides, and endothelial dysfunction in patients with coronary artery disease. Mol Cell Biochem 469, 29–39 (2020). https://doi.org/10.1007/s11010-020-03725-7

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