EP4 Agonist L-902,688 Suppresses EndMT and Attenuates Right Ventricular Cardiac Fibrosis in Experimental Pulmonary Arterial Hypertension
نویسندگان
چکیده
Right ventricular (RV) hypertrophy is characterized by cardiac fibrosis due to endothelial-mesenchymal transition (EndMT) and increased collagen production in pulmonary arterial hypertension (PAH) patients, but the mechanisms for restoring RV function are unclear. Prostanoid agonists are effective vasodilators for PAH treatment that bind selective prostanoid receptors to modulate vascular dilation. The importance of prostanoid signaling in the RV is not clear. We investigated the effects of the EP4-specific agonist L-902,688 on cardiac fibrosis and TGF-β-induced EndMT. EP4-specific agonist treatment reduced right ventricle fibrosis in the monocrotaline (MCT)-induced PAH rat model. L-902,688 (1 µM) attenuated TGF-β-induced Twist and α-smooth muscle actin (α-SMA) expression, but these effects were reversed by AH23848 (an EP4 antagonist), highlighting the crucial role of EP4 in suppressing TGF-β-induced EndMT. These data indicate that the selective EP4 agonist L-902,688 attenuates RV fibrosis and suggest a potential approach to reducing RV fibrosis in patients with PAH.
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عنوان ژورنال:
دوره 19 شماره
صفحات -
تاریخ انتشار 2018