Abstract
Background
Coronary artery disease (CAD), is the leading cause of mortality and morbidity worldwide. Tenascin-C (TNC) with high expression levels in inflammatory and cardiovascular diseases, leads to the rupture of atherosclerotic plaques. The origin of plaque destabilization can be associated to endothelial dysfunction. Given the high prevalence of CAD, finding valuable biomarkers for its early detection is of great interest. Using serum samples from patients with CAD and individuals without CAD, we assessed the efficacy of TNC expression levels in serum exosomes and during endothelial cell differentiation as a noninvasive biomarker of CAD.
Methods
TNC expression was analyzed using the RNA-sequencing data sets of 6 CAD and 6 normal samples of blood exosomes and endothelial differentiation transitions. Additionally, TNC expression was investigated in the serum samples of patients with CAD and individuals without CAD via qRT-PCR. ROC curve analysis was employed to test the suitability of TNC expression alterations as a CAD biomarker.
Results
TNC exhibited higher expression in the exosomes of the CAD samples than in those of the non-CAD samples. During endothelial differentiation, TNC expression was upregulated and then consistently downregulated in mature endothelial cells. Moreover, TNC was significantly upregulated in the serum of the CAD group (P = 0.02), with an AUC of 0.744 for the expression level (95% confidence interval, 0.582 to 0.907; P = 0.011). Hence its expression level can be discriminated CAD from non-CAD samples.
Discussion
Our study is the first to confirm that altered TNC expression is associated with pathological CAD conditions in Iranian patients. The expression of TNC is involved in endothelial differentiation and CAD development. Accordingly, TNC can serve as a valuable noninvasive biomarker with potential application in CAD diagnosis.
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Data Availability
Data and material are available on request from the correspondence author.
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Acknowledgements
The authors thank Dr Ali Sharifi-Zarchi for his kind assistance in data analysis. This work was supported by a research grant to Dr Malakootian awarded by the Research Deputyship of Rajaie Cardiovascular Medical and Research Center (94111).
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The study was approved by the ethics committee of Rajaie Cardiovascular Medical and Research Center “Mahshid Malakootian” (ethics code: RHC.ac.ir.REC.1396.61). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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11033_2022_7760_MOESM1_ESM.png
The image depicts the TNC expression levels in the three subgroups of CAD patients. The expression level of Tenascin-C (TNC) is not statistically significant between single vessel, two vessels and three vessels CAD patients (p > 0.05)
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Gholipour, A., Shakerian, F., Zahedmehr, A. et al. Tenascin-C as a noninvasive biomarker of coronary artery disease. Mol Biol Rep 49, 9267–9273 (2022). https://doi.org/10.1007/s11033-022-07760-z
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DOI: https://doi.org/10.1007/s11033-022-07760-z