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Int. J. Mol. Sci. 2018, 19(3), 727;

EP4 Agonist L-902,688 Suppresses EndMT and Attenuates Right Ventricular Cardiac Fibrosis in Experimental Pulmonary Arterial Hypertension

Department of Respiratory Therapy, Chang-Gung University College of Medicine, Tao-Yuan 33353, Taiwan
Cardiovascular Division, Chang Gung Memorial Hospital, Tao-Yuan 33353, Taiwan
Department of Respiratory Care, Chang-Gung University of Science and Technology, Chia-Yi 61363, Taiwan
Respiratory Therapy and Chest Medicine, Cathay General Hospital, Taipei 10630, Taiwan
Division of Thoracic Medicine, Chang Gung Memorial Hospital, Tao-Yuan 33353, Taiwan
Author to whom correspondence should be addressed.
Received: 22 January 2018 / Revised: 16 February 2018 / Accepted: 1 March 2018 / Published: 3 March 2018
(This article belongs to the Special Issue Molecular Research on Pulmonary Hypertension)
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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. View Full-Text
Keywords: right ventricular fibrosis; EP4 agonist; EndMT right ventricular fibrosis; EP4 agonist; EndMT

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Lai, Y.-J.; Chen, I.-C.; Li, H.-H.; Huang, C.-C. EP4 Agonist L-902,688 Suppresses EndMT and Attenuates Right Ventricular Cardiac Fibrosis in Experimental Pulmonary Arterial Hypertension. Int. J. Mol. Sci. 2018, 19, 727.

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