Fig. 5: PK/PD relationship and target engagement panel.
From: Preclinical development of a miR-132 inhibitor for heart failure treatment
a Tissue levels of antimiR-132 detected in the left ventricular (LV) remote region for different dosing groups of intracoronary/intravenous (ICIV) and intravenous/intravenous (IVIV) treated animals (Placebo: NaCl; Low = 1 mg/kg, Medium = 5 mg/kg and High = 10 mg/kg antimiR-132). b Correlation between antimiR-132 tissue levels and functional improvement (delta ejection fraction (EF) = EFday 56 – EFday 3). c Functional tissue level of miR-132 detected in the LV remote region. d Correlation between antimiR-132 and miR-132 tissue levels. e Target de-repression in the LV remote region after antimiR-132 treatment (Forkhead Box Protein O3, FOXO3; Sarcoplasmic/Endoplasmic Reticulum Ca2+ ATPase 2, SERCA2A; Endothelial Nitric Oxide Synthase 3, NOS3; SCL/TAL1 Interrupting Locus, STIL; TEK Receptor Tyrosine Kinase, TEK). Radar chart depicting the target engagement panel. ICIV and IVIV: Placebo: n = 22, Low dose: n = 20, Medium dose: n = 20, High dose: n = 17. Data are mean ± s.e.m; *P < 0.05, **P < 0.01, ***P < 0.001; Kruskal–Wallis test with Dunn’s multiple comparison and linear regression using non‐parametric Spearman correlation.
