Key result
ONO-1301 reduces pressure-overload cardiac fibrosis and LV dysfunction in mice by inhibiting TGF-β-induced FMT.
Why the study?
Fibroblast-to-myofibroblast transition is the primary inducer of cardiac fibrosis, and whether the synthetic prostacyclin agonist ONO-1301 attenuates pressure-overloaded cardiac fibrosis by modulating this transition was unknown.
Does ONO-1301 attenuate pressure-overloaded cardiac fibrosis by inhibiting fibroblast-to-myofibroblast transition in a murine model?
Does ONO-1301 attenuate pressure-overloaded cardiac fibrosis by inhibiting fibroblast-to-myofibroblast transition in a murine model?
The synthetic prostacyclin agonist ONO-1301 ameliorates pressure-overloaded cardiac fibrosis and dysfunction by inhibiting TGF-β-induced fibroblast-to-myofibroblast transition in a preclinical model.
Supports investigation of ONO-1301 in pressure-overload HF; leaves open translation from murine model to patients.
Fibroblast-to-myofibroblast transition (FMT) is the primary inducer of cardiac fibrosis. ONO-1301, a synthetic prostacyclin agonist, reportedly promotes tissue fibrosis repair by enhancing anti-fibrotic cytokine production. We hypothesized that ONO-1301 attenuates pressure-overloaded cardiac fibrosis by modulating FMT and generated a pressure-overloaded murine model via transverse aortic constriction (TAC) to evaluate the in vivo effects of ONO-1301. Cardiac fibrosis, left ventricular dilatation, and systolic dysfunction were established 4 weeks after TAC; however, ONO-1301 treatment initiated 2 weeks after TAC significantly attenuated those effects. Furthermore, ONO-1301 treatment significantly upregulated expression levels of cardioprotective cytokines such as vascular endothelial growth factor and hepatocyte growth factor in TAC hearts, whereas FMT-related factors, including transforming growth factor (TGF)-β1 and connective tissue growth factor, were significantly downregulated. The number of α-smooth muscle actin (α-SMA)- and vimentin-positive cells, representing fibroblast-originated cells transitioned into myofibroblasts, was significantly reduced in ONO-1301-treated TAC hearts. We isolated cardiac fibroblasts (CFs) from the left ventricles of adult male mice and assessed the effects of ONO-1301 on CFs stimulated by TGF-β. Results showed that ONO-1301 co-incubation significantly suppressed TGF-β-induced α-SMA expression and collagen synthesis, and significantly inhibited TGF-β-induced CF proliferation and migration. Our findings suggest that ONO-1301 ameliorates pressure overloaded cardiac fibrosis by inhibiting TGF-β-induced FMT.
No takes yet. Share an insight, caveat, or question.
Masada et al. (2020) studied Pressure-overloaded cardiac fibrosis. ONO-1301 vs. No ONO-1301 treatment was evaluated on Cardiac fibrosis, left ventricular dilatation, and systolic dysfunction. ONO-1301 significantly attenuated pressure-overloaded cardiac fibrosis, left ventricular dilatation, and systolic dysfunction in a murine model by inhibiting TGF-β-induced FMT.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: