Hidden scars on the heart, revealed by microRNA

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Here in the United States, our annual holiday celebrating romantic love is right around the corner. Whatever one’s opinion is about Valentine’s Day – overcommercialized and overrated, a sweet time to show appreciation, or just another day on the calendar – one can’t avoid the ubiquitous heart symbols in the shops. So in this heart-suffused environment, when I came across an exciting study about microRNAs as markers for diffuse myocardial fibrosis, I knew this was the right time to report on it.

Fibrosis is a huge problem in heart disease research, stemming from events like myocardial infarction and diseases like hypertrophic cardiomyopathy (HCM). The risks are serious – diffuse myocardial fibrosis factors into adverse outcomes like heart failure. While cardiac magnetic resonance (CMR) imaging can detect it, CMR is also expensive and not widely available, and it can’t be used in all patients. If researchers could find diagnostic markers in the blood, it would be a major step toward being able to noninvasively detect this condition.

Enter microRNAs, an RNA species that has exploded in recent years in the realm of circulating biomarker research. Fang and colleagues, reporting from the Baker IDI Heart and Diabetes Institute, note that a number of microRNAs are now known to be involved in regulating myocardial fibrosis, including miR-21, miR-29a, miR-30d and miR-133a. Could circulating microRNAs be effective biomarkers?

Their approach was straightforward:

– Recruit patients with HCM and asymmetric septal hypertrophy (excluding diabetes, cancer, etc.)

– Test for diffuse myocardial fibrosis using CMR (specifically, T1 mapping)

– Explore plasma microRNA link to diffuse myocardial fibrosis:
    – Profile microRNA in plasma from a small group (8 patients, 4 healthy controls) using a qPCR     array, then compare to CMR results
    – Test the larger cohort for the microRNAs that correlated to CMR results in the small group,
    using individual qPCR assays

– Determine a biomarker signature with ROC analysis

The team ultimately identified a signature of 8 microRNAs that could predict the presence of diffuse myocardial fibrosis with an AUC value of 0.87, a sensitivity of 81.5% and a specificity of 82.1%. The 8-microRNA signature for diffuse myocardial fibrosis identification includes:

  • – miR-18a-5p
  • – miR-30d-5p
  • – miR-21-5p
  • – miR-193-5p
  • – miR-10b-5p
  • – miR-15a-5p
  • – miR-296-5p
  • – miR-29a-3p

These are exciting findings in a couple of different ways. The most obvious, of course, is in the potential translational use of this signature – in the future, this signature or another like it could replace CMR, diagnosing individuals with diffuse myocardial fibrosis effectively in a lower-cost, more accessible way. Beyond this, there’s also the basic biology underlying why these microRNAs circulate – which cells release them, and what are they released to do? The answers to these questions could help researchers better understand the processes by which fibrosis forms in the heart.

Want to know more about profiling microRNAs from biofluids? Download your copy of the webinar,  “Biofluid miRNA Profiling: From Sample to Biomarker”!

Reference:

1. Fang, L. et al. (2015) Circulating microRNAs as biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy. J. Transl. Med. 13, 314. Link

Ali Bierly

Ali Bierly, PhD is a Global Market Manager in Translational Sciences at QIAGEN, and has written on a number of scientific topics in the biotech industry as the author of QIAGEN's Reviews Online. She received her PhD from Cornell University in 2009, studying the immune response to a protozoan parasite, Toxoplasma gondii. Ali has a keen interest in the emerging importance of microRNA and other circulating nucleic acids as biomarkers for disease.

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