122 Non-coding rnas versus protein biomarkers for early detection of myocardial injury

Rationale Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNA) and long non-coding RNAs (lncRNA), have been implicated as novel cardiac biomarkers. Objective To compare the tissue-specificity and release kinetics of ncRNAs and protein biomarkers after induced myocardial injury by transcoronary ablation of septal hypertrophy (TASH). Methods and results Upon screening the relative abundance of 109 circRNA and 21 lncRNAs in human cardiac tissue, 12 circRNAs and 11 lncRNAs were selected for further analyses. Human myocardial tissue was spiked into plasma from healthy individuals and the expression levels of ncRNAs were compared to a panel of miRNAs, including muscle- (miR-1, miR-133a) and cardiac-enriched miRNAs (miR-208a, miR-208b, miR-499). Curve fitting analyses of each of the three ncRNA classes with the highest R2 values revealed no significant differences in the regression coefficients compared with high sensitive troponin T and I (hs-cTnT, hs-cTnI) and cardiac myosin-binding protein C (cMyC). At low spike-in concentrations, however, significantly higher regression coefficients were observed for all ncRNA species (Mann Whitney test: miRNAs vs. proteins p Conclusions Our results demonstrate that circulating heart-associated ncRNAs may enhance early detection of myocardial injury. All three ncRNA classes demonstrated superior release kinetics in vitro compared with established cardiac protein biomarkers. At early time points after TASH, however, a higher sensitivity was only observed for muscle-enriched miRNAs, but not for circRNAs or lncRNAs.