Upregulation of Circulating Cardiomyocyte-Enriched miR-1 and miR-133 Associate with the Risk of Coronary Artery Disease in Type 2 Diabetes Patients and Serve as Potential Biomarkers

Abstract

Circulating miRNAs are increasingly suggested as clinical biomarker for diseases. We evaluated the expression of circulating cardiomyocyte-enriched miR-1 and miR-133 by real-time PCR in blood from patients with type 2 diabetes (T2D) without and with coronary artery disease (CAD) and healthy controls, investigated their association with the risk of CAD risk and their potential as biomarkers. The two miRNAs were upregulated in patients with T2D and CAD compared with controls, associated with CAD risk and remained significant after adjustment for multiple confounders. LDL-C was a positive predictor for miR-1 and miR-133, and mean blood pressure was also a positive predictor for miR-133. Both miRNAs strongly distinguished CAD from controls. miR-1 significantly distinguished CAD from T2D with higher diagnostic ability than miR-133, whereas the miR-1/miR-133 combination improved the diagnostic value. Upregulation of circulating miR-1 and miR-133 associate with the risk of CAD in T2D patients and may serve as diagnostic biomarkers.

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Abbreviations

LDL-C:

Low-density lipoprotein cholesterol

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Acknowledgments

We would like to acknowledge the technical support of the Research Unit staff at Al-Jawhara Centre for Molecular Medicine, Genetics and Inherited Disorders in the College of Medicine and Medical Sciences, Arabian Gulf University.

Funding

The present study was supported by a research grant (No. 81) by the College of Medicine and Medical Sciences, Arabian Gulf University, Kingdom of Bahrain and a PhD Research Grant by Kingdom of Saudi Arabia.

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Correspondence to Ghada Al-Kafaji.

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The authors declare that they have no conflict of interest.

Ethical Approval

Ethical approval to conduct the current study was obtained from the Medical Research and Ethics Committee in the College of Medicine and Medical Sciences, Arabian Gulf University, Kingdom of Bahrain. The participants were given a complete description of the study, and provided written informed consents according to the guidelines of the College of Medicine and Medical Sciences, Arabian Gulf University, Kingdom of Bahrain.

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Clinical Relevance of the Study

• Currently, there are no biomarkers for early detection of type 2 diabetes-associated macrovascular complications.

• Circulating miRNAs are increasingly suggested as clinical biomarker for several diseases.

• We show that the upregulation of circulating cardiomyocyte-enriched miR-1 and miR-133 are associated with the risk of coronary artery disease in type 2 diabetes patients and could serve as diagnostic biomarkers.

Associate Editor Craig Stolen oversaw the review of this article

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Al-Muhtaresh, H.A., Salem, A.H. & Al-Kafaji, G. Upregulation of Circulating Cardiomyocyte-Enriched miR-1 and miR-133 Associate with the Risk of Coronary Artery Disease in Type 2 Diabetes Patients and Serve as Potential Biomarkers. J. of Cardiovasc. Trans. Res. 12, 347–357 (2019). https://doi.org/10.1007/s12265-018-9857-2

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Keywords

  • Circulating miRNAs
  • Type 2 diabetes
  • Coronary artery disease
  • Biomarkers