Introduction: Heart failure due to hypertrophic heart disease is a life-threatening disorder worldwide.
Synthetic prostacyclin agonist (YS-1402) has been reported to have impact on myocardial
repair by enhancement of production in various cytokines. We hypothesized that YS-1402
might attenuate the pressure overload-induced cardiac remodeling. Methods: Adult male mice underwent transverse aortic constriction (TAC) surgery and YS-1402
(5 mg/kg) was subcutaneously injected at 2 weeks after the TAC (n = 8). Results: The heart-to-body weight ratio at 4 weeks after TAC was significantly lower in the
YS group than in the vehicle group (6.1 ± 0.4 mg/g vs. 11.3 ± 0.7 mg/g; P < .01) and YS-1402 significantly improved the systolic function. Picrosirius red
staining demonstrated that left ventricular fibrosis significantly decreased in the
YS group (Fibrotic area: 3.0 ± 1.3% vs. 6.1 ± 2.3%; P < .01). Moreover, mRNA expression levels of collagen I (1.8 ± 0.5 vs. 6.0 ± 1.9;
P < .01), collagen III (1.6 ± 0.4 vs. 5.5 ± 2.1; P < .01), TGF-β (1.3 ± 0.2 vs. 1.9 ± 0.4; P = .02), and CTGF (3.5 ± 1.4 vs. 12.0 ± 4.4; P < .01) were significantly lower in the YS group. Conclusions: YS-1402 attenuates the pressure overload-induced cardiac hypertrophy and fibrosis,
suggesting therapeutic potentials in heart failure due to hypertrophic heart disease.
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