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9 Micrornas Represent Novel Biological Markers of Coronary Artery Calcification
  1. Philippa Howlett1,
  2. Abdul Waheed2,
  3. Alex Horton3,
  4. Nikunj Shah2,
  5. Edward Leatham4,
  6. Huihai Wu2,
  7. Andre Gerber2,
  8. Michael Mahmoudi2
  1. 1University of Surrey
  2. 2The University of Surrey
  3. 3Royal Surrey County Hospital
  4. 4The Royal Surrey County Hospital

Abstract

Introduction Conventional risk stratification fails to identify many individuals presenting with major adverse cardiovascular events (MACE). Coronary artery calcification (CAC) is a powerful independent predictor of MACE however its use is limited by radiation and expense. MicroRNAs are non-coding RNAs that regulate transcription and their differential expression is acknowledged to be a hallmark of a number of diseases. We aim to determine if a peripheral blood-based microRNA profile is predictive of the presence and extent of CAC in humans.

Methods Study patients met the following inclusion criteria: attendance for elective cardiac computed tomography; age 18–65 years; no history of coronary artery disease, cardiomyopathy or tachyarrhythmia; normal renal function; no history of diabetes mellitus; no autoimmune disease; no infection; no malignancy. Peripheral venesection was performed and an Agatston score was derived using default software. RNA was extracted using the LeukoLOCK Total RNA Isolation System and stored at –80oC until Toray’s microarray analysis was undertaken.

Results 24 participants were recruited (mean age 54 years; 67% male) and divided into the following categories: [CAC score 0] n = 6; [CAC score 1–10] n = 6; [CAC score 11–100] n = 6; [CAC score > 100] n = 6. Groups were matched according to their baseline characteristics; Table 1. The Student’s t-test was performed between groups. MiR-1181 was significantly down-regulated in all case groups compared to controls: [CAC 1–10] effect size (ES) = 1.76, p = 0.012; [CAC 11–100] ES = 1.74, p = 0.013; [CAC > 100] ES = 3.86, p < 0.01. Furthermore miR-138-2-3p, miR-6816-3p and miR-8059 were expressed less in those with a CAC score > 100 compared to controls (ES = 3, p < 0.001; ES = 2.87, p < 0.001; ES = 2.6, p = 0.001 respectively); Figure 1.

Abstract 9 Table 1

Patient baseline characteristics by group

Abstract 9 Figure 1

A heatmap of expression for miR-6816-3p, miR-1181, miR-138-2-3p and miR-8059. The expression range ‘low-moderate-high’ is indicated by the colour range ‘blue-white-red’

Conclusions Human blood-based miRNA-1181 appears to predict the presence and extent of CAC. Likewise miRNAs miR-138-2-3p, miR-6816-3p and miR-8059 are differentially expressed in patients with high CAC scores. We plan to validate these findings using quantitative real-time PCR and to test these results in a prospective cohort. Ultimately miRNAs could act as a biomarker for MACE and identifying their associated molecular pathways may explain the mechanisms underpinning CAC.

  • microRNAs
  • coronary artery calcification
  • biomarker

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