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Eric Mick1, Ravi Shah1, Kahraman Tanriverdi1

  • 1From the Department of Quantitative Health Sciences (E.M.) and Department of Medicine (K.T., J.E.F.), University of Massachusetts Medical School, Worcester; Department of Cardiology, Massachusetts General Hospital, Boston (R.S.); Department of Cardiology, University of Michigan, Ann Arbor (V.M.); Yale University Medical School, Computational Biology, New Haven, CT (M.G., J.R., R.K.); The NHLBI's and Boston University's Framingham Heart Study, MA (M.G.L.); Biostatistics Department, Boston University School of Public Health, MA (M.G.L.); and The Framingham Heart Study, Population Sciences Branch, NHLBI, Bethesda, MD (D.L.).

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|March 15, 2017
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Summary
This summary is machine-generated.

This study found seven extracellular RNAs (ex-RNAs) linked to stroke risk in the Framingham Heart Study cohort. These findings highlight ex-RNAs, including microRNAs, as potential biomarkers for stroke, distinct from coronary heart disease.

Keywords:
RNAscardiovascular diseasesgenesrisk factorsstroke

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Area of Science:

  • Molecular Biology
  • Genomics
  • Cardiovascular Research

Background:

  • Growing interest in extracellular RNAs (ex-RNAs) and their association with cardiovascular diseases.
  • Previous studies on ex-RNAs and cardiovascular disease risk were limited by small sample sizes and candidate-based miRNA analysis.
  • Lack of human studies investigating novel ex-RNAs and their link to stroke.

Purpose of the Study:

  • To conduct an unbiased investigation of extracellular RNAs (ex-RNAs) in relation to stroke and coronary heart disease (CHD) risk.
  • To explore associations between a broad range of ex-RNAs, including microRNAs (miRNAs), small nucleolar RNAs (snoRNAs), and piwi-interacting RNAs (piRNAs), and stroke/CHD.
  • To determine if ex-RNAs are associated with prevalent and incident stroke and CHD in a large observational cohort.

Main Methods:

  • Unbiased next-generation sequencing of plasma from 40 Framingham Heart Study (FHS) participants.
  • High-throughput polymerase chain reaction (PCR) analysis of 471 ex-RNAs in 2763 additional FHS participants.
  • Exploration of associations between 331 miRNAs, 43 snoRNAs, and 97 piRNAs with prevalent and incident stroke and CHD.

Main Results:

  • Seven extracellular RNAs (ex-RNAs) were significantly associated with stroke prevalence or incidence after adjusting for cardiovascular disease risk factors.
  • No significant associations were found between any ex-RNAs and prevalent or incident coronary heart disease.
  • The identified ex-RNA associations with stroke were specific, with no overlap between prevalent and incident stroke events.

Conclusions:

  • This is the largest unbiased study to date examining ex-RNAs in relation to stroke in an observational cohort.
  • The study is the first large-scale investigation of human small noncoding RNAs beyond microRNAs in relation to stroke.
  • Extracellular RNAs, particularly microRNAs, are associated with stroke risk in a large observational cohort.