An increase in certain microRNAs (miRNAs) circulating in the blood indicates injury to cardiac muscle, according to a study published online July 10 in the Proceedings of the National Academy of Sciences. While protein biomarkers, namely cardiac troponin, have served as the basis for diagnostic and prognostic evaluation of patients with heart muscle injury, the authors say that use of mRNAs may prove to be more sensitive and in the future may provide the basis for a “universal” test, rather than current assessment of single proteins. The researchers compared the composition of miRNAs in a cohort of patients with stable and advanced heart failure (HF; n = 35) to the composition of eight normal adult and five fetal samples. Heart failure patients were examined both before and after treatment with a left ventricular assist device (LVAD). The researchers identified three RNAs, known to originate in the heart, with potential for use as markers of heart injury. Heart- and muscle-specific circulating miRNAs (myomirs) increased up to 140-fold in advanced HF, which coincided with a similar increase in cardiac troponin I (cTnI). Three months after initiation of LVAD support, these extracellular changes nearly completely reversed. There was less than a fivefold difference […]
An increase in certain microRNAs (miRNAs) circulating in the blood indicates injury to cardiac muscle, according to a study published online July 10 in the Proceedings of the National Academy of Sciences. While protein biomarkers, namely cardiac troponin, have served as the basis for diagnostic and prognostic evaluation of patients with heart muscle injury, the authors say that use of mRNAs may prove to be more sensitive and in the future may provide the basis for a “universal” test, rather than current assessment of single proteins.
The researchers compared the composition of miRNAs in a cohort of patients with stable and advanced heart failure (HF; n = 35) to the composition of eight normal adult and five fetal samples. Heart failure patients were examined both before and after treatment with a left ventricular assist device (LVAD).
The researchers identified three RNAs, known to originate in the heart, with potential for use as markers of heart injury. Heart- and muscle-specific circulating miRNAs (myomirs) increased up to 140-fold in advanced HF, which coincided with a similar increase in cardiac troponin I (cTnI). Three months after initiation of LVAD support, these extracellular changes nearly completely reversed. There was less than a fivefold difference in levels of circulating miRNAs among stable HF patients, compared with normal patients, while myomir and cTnI levels were only captured near the detection limit.
While disappointed at the relatively low levels of heart-specific circulating miRNAs, the authors do believe miRNAs afford advantages over cardiac troponin, including that the protein complexes containing miRNA are fully soluble and may be more rapidly released into circulation, compared to troponin, which is heavily bound to heart muscle filaments. Additionally, they believe enough evidence exists to justify further research in the diagnostic value of miRNAs, which they believe will lead eventually to a more “universal” test, encompassing a cluster of miRNAs, rather than the current evaluation of single proteins.
“Our findings provide the underpinning for miRNA-based therapies and emphasize the usefulness of circulating miRNAs as biomarkers for heart injury,” writes senior author P. Christian Schulze, M.D., Ph.D., from Columbia University Medical Center (New York). “The translation of this type of RNAseq assay into clinical practice is currently limited by the time required for cDNA library preparation and sequencing, however, single-molecule direct RNAseq or targeted RT-PCR assays may overcome some of these limitations.”
Takeaway: While miRNAs are not currently ready for use as a marker of heart muscle injury, researchers believe that within the next five years they will be integrated in panel formats, rather than relying on current tests of single protein markers.
