Blockade of miR-140-3p prevents functional deterioration in afterload-enhanced engineered heart tissue

Blockade of miR-140-3p prevents functional deterioration in afterload-enhanced engineered heart tissue

Blog Article

Abstract Afterload enhancement (AE) of rat engineered heart tissue (EHT) in vitro leads to a multitude of changes that in vivo are referred to as pathological cardiac hypertrophy: e.g., cardiomyocyte hypertrophy, contractile dysfunction, reactivation of fetal genes and fibrotic changes.Moreover AE induced the upregulation of 22 abundantly expressed microRNAs.

Here, we aimed at evaluating the functional effect of inhibiting 7 promising microRNAs (miR-21-5p, miR-146b-5p, miR-31a-5p, miR-322-5p, miR-450a-5p, miR-140-3p and miR-132-3p) in a small-range screen.Singular transfection of locked nucleic acid (LNA)-based anti-miRs at 100 nM (before the one week AE-procedure) led to a powerful reduction of the targeted tonies jj audio play character from cocomelon microRNAs.Pretreatment with anti-miR-146b-5p, anti-miR-322-5p or anti-miR-450a-5p did not alter the AE-induced contractile decline, while anti-miR-31a-5p-pretreatment even worsened it.Anti-miR-21-5p and anti-miR-132-3p partially attenuated the AE-effect, confirming previous reports.

LNA-anti-miR against miR-140-3p, a microRNA recently identified as a prognostic biomarker of cardiovascular disease, also attenuated the AE-effect.To simplify future in vitro experiments and to create an inhibitor for in vivo applications, we designed shorter miR-140-3p-inhibitors and encountered variable efficiency.Only the inhibitor that effectively repressed miR-140-3p was also protective against the AE-induced contractile decline.In summary, in a small-range functional screen, miR-140-3p evolved as a possible new target for the attenuation of afterload-induced lifewalker upwalker pathological cardiac hypertrophy.