dc.contributor.author | Patel, Jigisha | |
dc.contributor.author | Abdelazeem, Heba | |
dc.contributor.author | Bouhadoun, Amel | |
dc.contributor.author | Yung, Sonia | |
dc.contributor.author | Li, Fangfang | |
dc.contributor.author | Mahieddine, Youcef | |
dc.contributor.author | Silverstein, Adam M. | |
dc.contributor.author | Castier, Yves | |
dc.contributor.author | Cazes, Aurelie | |
dc.contributor.author | Clapp, Lucie H. | |
dc.contributor.author | Norel, Xavier | |
dc.contributor.author | Longrois, Dan | |
dc.contributor.author | Ozen, Gulsev | |
dc.contributor.author | Benyahia, Chabha | |
dc.contributor.author | Amgoud, Yasmine | |
dc.date.accessioned | 2021-03-04T11:13:35Z | |
dc.date.available | 2021-03-04T11:13:35Z | |
dc.identifier.citation | Ozen G., Benyahia C., Amgoud Y., Patel J., Abdelazeem H., Bouhadoun A., Yung S., Li F., Mahieddine Y., Silverstein A. M. , et al., "Interaction between PGI(2) and ET-1 pathways in vascular smooth muscle from Group-III pulmonary hypertension patients", PROSTAGLANDINS & OTHER LIPID MEDIATORS, cilt.146, 2020 | |
dc.identifier.issn | 1098-8823 | |
dc.identifier.other | av_713a6b61-3141-4929-9f74-5a27d5cf73b2 | |
dc.identifier.other | vv_1032021 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12627/78011 | |
dc.identifier.uri | https://doi.org/10.1016/j.prostaglandins.2019.106388 | |
dc.description.abstract | Pulmonary hypertension (PH) is characterized by an elevation of mean pulmonary artery pressure and it is classified into five groups. Among these groups, PH Group-III is defined as PH due to lung disease or hypoxia. Prostacyclin (PGI(2)) analogues (iloprost, treprostinil) and endothelin-1 (ET-1) receptor antagonists (ERA) (used alone or in combination) are therapies used for treating PH. The mechanisms underlying the positive/negative effects of combination treatment are not well documented, and in this study, we tested the hypothesis that the combination of a PGI(2) analogue (iloprost, treprostinil) and an ERA may be more effective than either drug alone to treat vasculopathies observed in PH Group-III patients. Using Western blotting, ETA and ETB receptor expression were determined in human pulmonary artery (HPA) preparations derived from control and PH Group-III patients, and the physiologic impact of altered expression ratios was assessed by measuring ET-1 induced contraction of ex vivo HPA and human pulmonary veins (HPV) in an isolated organ bath system. In addition, the effects of single agent or combination treatments with a PGI(2) analogue and an ERA on ET-1 release and HPA smooth muscle cells (hPASMCs) proliferation were determined by ELISA and MTT techniques, respectively. Our results indicate that the increased ETA/ETB receptor expression ratio in HPA derived from PH Group-III patients is primarily governed by a greatly depressed ETB receptor expression. However, contractions induced by ET-1 are not impacted in HPA and HPV derived from PH Group-III patients as compared to controls. Also, we found that the combination of an ETA receptor antagonist (BQ123) with iloprost provides greater inhibition of hPASMCs proliferation (-48 +/- 14% control; -32 +/- 06% PH) than either agent alone. Of note, while the ETB receptor antagonist (BQ788) increases ET-1 production from PH Group-III patients' preparations (HPA, parenchyma), even under these more proliferative conditions, iloprost and treprostinil are still effective to inhibit hPASMCs proliferation (-22/-24%). Our findings may provide new insights for the treatment of PH Group-III by combining a PGI(2) analogue and a selective ETA receptor antagonist. | |
dc.language.iso | eng | |
dc.subject | Histoloji-Embriyoloji | |
dc.subject | BİYOKİMYA VE MOLEKÜLER BİYOLOJİ | |
dc.subject | Moleküler Biyoloji ve Genetik | |
dc.subject | Yaşam Bilimleri (LIFE) | |
dc.subject | HÜCRE BİYOLOJİSİ | |
dc.subject | Tıp | |
dc.subject | Sağlık Bilimleri | |
dc.subject | Temel Tıp Bilimleri | |
dc.subject | Yaşam Bilimleri | |
dc.subject | Moleküler Biyoloji ve Genetik | |
dc.subject | Sitogenetik | |
dc.subject | Temel Bilimler | |
dc.title | Interaction between PGI(2) and ET-1 pathways in vascular smooth muscle from Group-III pulmonary hypertension patients | |
dc.type | Makale | |
dc.relation.journal | PROSTAGLANDINS & OTHER LIPID MEDIATORS | |
dc.contributor.department | Assistance Publique Hopitaux Paris (APHP) , , | |
dc.identifier.volume | 146 | |
dc.contributor.firstauthorID | 273492 | |