MicroRNA 8059 as a marker for the presence and extent of coronary artery calcification

Philippa Howlett, Jane K Cleal, Huihai Wu, Nikunj Shah, Alex Horton, Nick Curzen, Michael Mahmoudi, Philippa Howlett, Jane K Cleal, Huihai Wu, Nikunj Shah, Alex Horton, Nick Curzen, Michael Mahmoudi

Abstract

Objective: MicroRNAs (miRNAs) may serve as potential biomarkers in a variety of pathologies. The aim of this study was to determine whether miRNAs could serve as blood-based markers of isolated coronary artery calcification (CAC) defined as CAC in the absence of an underlying metabolic abnormality.

Methods: 24 age-matched and sex-matched patients who had been referred for elective CT coronary calcium score and angiography as part of investigation for cardiac chest pain were recruited. Peripheral venesection was performed and an Agatston calcium score was derived from the CT coronary angiogram using default software. RNA was extracted using the LeukoLOCK Total RNA Isolation System for Toray's microarray analysis and quantitative reverse transcription PCR (qRT-PCR).

Results: The patients were well matched for age, sex and conventional risk factors for coronary artery disease. Microarray analysis identified lower expression of miRNA-138-2-3p, miRNA-1181, miRNA-6816-3p and miRNA-8059 in patients with coronary artery calcium score (CACS)=0 vs CACS>100. qRT-PCR confirmed significant downregulation of miRNA-8059 in patients with CACS>100 (CACS=0 vs CACS>100; P=0.03).

Conclusion: miRNA-8059 may serve as a peripheral blood-based biomarker for the presence of CAC, as well as provide a platform for studying the pathophysiological basis of isolated CAC.

Trial registration number: NCT01992848; Results.

Keywords: Coronary artery calcification; coronary artery calcium score; microRNA.

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Toray microarray analysis of the four groups of patients (A) and in patients with calcium score >100 (B). These data indicate that the expression of four microRNAs is significantly reduced in patients with calcium score >100 compared with controls: miRNA-138-2-3p, miRNA-1181, miRNA-6816-3p and miRNA-8059. Data are presented as mean±SEM. Ca, calcium.
Figure 2
Figure 2
Heat map of microRNA microarray expression from the four groups of patients. The expression range ‘low-moderate-high’ is indicated by the colour range ‘blue-white-red’. The upper colour bar represents the groups as follows: yellow for CACS=0, green for CACS=1–10, red for CACS=11–100 and blue for CACS>100. CACS, coronary artery calcium score.
Figure 3
Figure 3
Quantitative reverse transcription PCR analysis indicated significant downregulation of miR-8059 in patients with coronary artery calcification score>100 (P=0.03). Ca, calcium.

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