Phosphodiesterase 10A upregulation contributes to pulmonary vascular remodeling.

Phosphodiesterases (PDEs) modulate the cellular proliferation involved in the pathophysiology of pulmonary hypertension (PH) by hydrolyzing cAMP and cGMP. The present study was designed to determine whether any of the recently identified PDEs (PDE7-PDE11) contribute to progressive pulmonary vascular...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xia Tian, Christina Vroom, Hossein Ardeschir Ghofrani, Norbert Weissmann, Ewa Bieniek, Friedrich Grimminger, Werner Seeger, Ralph Theo Schermuly, Soni Savai Pullamsetti
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc3666364c04487bb3c389b232a4e9ec
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cc3666364c04487bb3c389b232a4e9ec
record_format	dspace
spelling	oai:doaj.org-article:cc3666364c04487bb3c389b232a4e9ec2021-11-18T06:55:56ZPhosphodiesterase 10A upregulation contributes to pulmonary vascular remodeling.1932-620310.1371/journal.pone.0018136https://doaj.org/article/cc3666364c04487bb3c389b232a4e9ec2011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21494592/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Phosphodiesterases (PDEs) modulate the cellular proliferation involved in the pathophysiology of pulmonary hypertension (PH) by hydrolyzing cAMP and cGMP. The present study was designed to determine whether any of the recently identified PDEs (PDE7-PDE11) contribute to progressive pulmonary vascular remodeling in PH. All in vitro experiments were performed with lung tissue or pulmonary arterial smooth muscle cells (PASMCs) obtained from control rats or monocrotaline (MCT)-induced pulmonary hypertensive (MCT-PH) rats, and we examined the effects of the PDE10 inhibitor papaverine (Pap) and specific small interfering RNA (siRNA). In addition, papaverine was administrated to MCT-induced PH rats from day 21 to day 35 by continuous intravenous infusion to examine the in vivo effects of PDE10A inhibition. We found that PDE10A was predominantly present in the lung vasculature, and the mRNA, protein, and activity levels of PDE10A were all significantly increased in MCT PASMCs compared with control PASMCs. Papaverine and PDE10A siRNA induced an accumulation of intracellular cAMP, activated cAMP response element binding protein and attenuated PASMC proliferation. Intravenous infusion of papaverine in MCT-PH rats resulted in a 40%-50% attenuation of the effects on pulmonary hypertensive hemodynamic parameters and pulmonary vascular remodeling. The present study is the first to demonstrate a central role of PDE10A in progressive pulmonary vascular remodeling, and the results suggest a novel therapeutic approach for the treatment of PH.Xia TianChristina VroomHossein Ardeschir GhofraniNorbert WeissmannEwa BieniekFriedrich GrimmingerWerner SeegerRalph Theo SchermulySoni Savai PullamsettiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 4, p e18136 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xia Tian Christina Vroom Hossein Ardeschir Ghofrani Norbert Weissmann Ewa Bieniek Friedrich Grimminger Werner Seeger Ralph Theo Schermuly Soni Savai Pullamsetti Phosphodiesterase 10A upregulation contributes to pulmonary vascular remodeling.
description	Phosphodiesterases (PDEs) modulate the cellular proliferation involved in the pathophysiology of pulmonary hypertension (PH) by hydrolyzing cAMP and cGMP. The present study was designed to determine whether any of the recently identified PDEs (PDE7-PDE11) contribute to progressive pulmonary vascular remodeling in PH. All in vitro experiments were performed with lung tissue or pulmonary arterial smooth muscle cells (PASMCs) obtained from control rats or monocrotaline (MCT)-induced pulmonary hypertensive (MCT-PH) rats, and we examined the effects of the PDE10 inhibitor papaverine (Pap) and specific small interfering RNA (siRNA). In addition, papaverine was administrated to MCT-induced PH rats from day 21 to day 35 by continuous intravenous infusion to examine the in vivo effects of PDE10A inhibition. We found that PDE10A was predominantly present in the lung vasculature, and the mRNA, protein, and activity levels of PDE10A were all significantly increased in MCT PASMCs compared with control PASMCs. Papaverine and PDE10A siRNA induced an accumulation of intracellular cAMP, activated cAMP response element binding protein and attenuated PASMC proliferation. Intravenous infusion of papaverine in MCT-PH rats resulted in a 40%-50% attenuation of the effects on pulmonary hypertensive hemodynamic parameters and pulmonary vascular remodeling. The present study is the first to demonstrate a central role of PDE10A in progressive pulmonary vascular remodeling, and the results suggest a novel therapeutic approach for the treatment of PH.
format	article
author	Xia Tian Christina Vroom Hossein Ardeschir Ghofrani Norbert Weissmann Ewa Bieniek Friedrich Grimminger Werner Seeger Ralph Theo Schermuly Soni Savai Pullamsetti
author_facet	Xia Tian Christina Vroom Hossein Ardeschir Ghofrani Norbert Weissmann Ewa Bieniek Friedrich Grimminger Werner Seeger Ralph Theo Schermuly Soni Savai Pullamsetti
author_sort	Xia Tian
title	Phosphodiesterase 10A upregulation contributes to pulmonary vascular remodeling.
title_short	Phosphodiesterase 10A upregulation contributes to pulmonary vascular remodeling.
title_full	Phosphodiesterase 10A upregulation contributes to pulmonary vascular remodeling.
title_fullStr	Phosphodiesterase 10A upregulation contributes to pulmonary vascular remodeling.
title_full_unstemmed	Phosphodiesterase 10A upregulation contributes to pulmonary vascular remodeling.
title_sort	phosphodiesterase 10a upregulation contributes to pulmonary vascular remodeling.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/cc3666364c04487bb3c389b232a4e9ec
work_keys_str_mv	AT xiatian phosphodiesterase10aupregulationcontributestopulmonaryvascularremodeling AT christinavroom phosphodiesterase10aupregulationcontributestopulmonaryvascularremodeling AT hosseinardeschirghofrani phosphodiesterase10aupregulationcontributestopulmonaryvascularremodeling AT norbertweissmann phosphodiesterase10aupregulationcontributestopulmonaryvascularremodeling AT ewabieniek phosphodiesterase10aupregulationcontributestopulmonaryvascularremodeling AT friedrichgrimminger phosphodiesterase10aupregulationcontributestopulmonaryvascularremodeling AT wernerseeger phosphodiesterase10aupregulationcontributestopulmonaryvascularremodeling AT ralphtheoschermuly phosphodiesterase10aupregulationcontributestopulmonaryvascularremodeling AT sonisavaipullamsetti phosphodiesterase10aupregulationcontributestopulmonaryvascularremodeling
_version_	1718424195062300672

Phosphodiesterase 10A upregulation contributes to pulmonary vascular remodeling.

Ejemplares similares