MicroRNA-126 in Cardiovascular Disease - from Phenotype to Molecular Function

• Applicant: Dr. Christian Schulte
• Subject Area: Cardiology, Angiology ; Cell Biology
• Term: from 2016 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 328550563

• Final Report Year: 2019

Final Report Abstract

In summary, heparinase treatment is essential when evaluating ncRNAs in clinical settings. Amongst ncRNAs, cardiac miRNAs remained the best predictor for the diagnosis of acute MI. In serial samples from TASH and acute MI patients, cardiac miRNAs showed comparable AUC values to hs-cTnT and the additional use of muscle-enriched miRNAs combined with hs-cTnT and cMyBP-C returned the highest AUC in the clinical setting of MI, pointing out their potential future use in combined protein/ncRNA biomarker approaches. On the other hand, miRNA sensitivity proved to be well below hs-cTnT, arguing against their clinical application at the current stage of methodological advances. Thus, analyses in larger cohorts seem warranted once technological advances offer better sensitivity. Future miRNA assays also require faster, automated quantification if miRNAs were to be used for complementing protein biomarkers. With regards to cardiac proteins, measurements of cMyBP-C could offer some of the benefits of miRNAs, as evidenced by an earlier rise and faster decline after myocardial injury and a better baseline detectability compared to cardiac troponins. Surprisingly, for almost one decade, miRNAs have been assessed as potential biomarkers for the detection of myocardial infarction, but none of the publications have taken heparin into account as a confounder of noncoding RNA quantification. Having presented the effectiveness of heparinase treatment in clinical samples opens up a new path to enable integration of noncoding RNA measurements in clinical settings.

Publications

• 2018. Inhibition of profibrotic microRNA-21 affects platelets and their releasate. JCI insight 3
  Barwari, T., Eminaga, S., Mayr, U., Lu, R., Armstrong, P.C., Chan, M. V, Sahraei, M., Fernández-Fuertes, M., Moreau, T., Barallobre-Barreiro, J., Lynch, M., Yin, X., Schulte, C., Baig, F., Pechlaner, R., Langley, S.R., Zampetaki, A., Santer, P., Weger, M., Plasenzotti, R., Schosserer, M., Grillari, J., Kiechl, S., Willeit, J., Shah, A.M., Ghevaert, C., Warner, T.D., Fernández-Hernando, C., Suárez, Y., Mayr, M.
  
• 2019. Comparative Analysis of Circulating Non-Coding RNAs Versus Protein Biomarkers in the Detection of Myocardial Injury. Circ. Res.CIRCRESAHA.119.314937
  Schulte, C., Barwari, T., Joshi, A., Theofilatos, K., Zampetaki, A., Barallobre-Barreiro, J., Singh, B., Sörensen, N.A., Neumann, J.T., Zeller, T., Westermann, D., Blankenberg, S., Marber, M., Liebetrau, C., Mayr, M.
  
• 2019. MicroRNAs: A New Understanding of Platelet Physiology and Pathology. Thromb Haemost. Feb;119(2):191
  Schulte, C. Mayr M.