Publication Name	World Journal of Gastroenterology
Manuscript ID	40791
Country	Germany

Received	2018-07-16 05:07
Peer-Review Started	2018-07-16 07:15
First Decision by Editorial Office Director	2018-08-01 01:12
Return for Revision	2018-08-01 08:06
Revised	2018-08-03 15:14
Publication Fee Transferred
Second Decision by Editor	2018-08-20 06:57
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2018-08-24 09:10
Articles in Press	2018-08-24 09:10
Edit the Manuscript by Language Editor
Typeset the Manuscript	2018-10-10 01:53
Publish the Manuscript Online	2018-10-12 05:32

ISSN	1007-9327 (print) and 2219-2840 (online)
Open Access	This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Copyright	© The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Article Reprints	For details, please visit: http://www.wjgnet.com/bpg/gerinfo/247
Permissions	For details, please visit: http://www.wjgnet.com/bpg/gerinfo/207
Publisher	Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Website	http://www.wjgnet.com

Category	Gastroenterology & Hepatology
Manuscript Type	Basic Study
Article Title	Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension
Manuscript Source	Invited Manuscript
All Author List	Denise Schaffner, Adhara Lazaro, Peter Deibert, Peter Hasselblatt, Patrick Stoll, Lisa Fauth, Manfred W Baumstark, Irmgard Merfort, Annette Schmitt-Graeff and Wolfgang Kreisel
ORCID	Author(s) ORCID Number Denise Schaffner http://orcid.org/0000-0001-6173-9288 Adhara Lazaro http://orcid.org/0000-0001-9023-1387 Peter Deibert http://orcid.org/0000-0002-3291-884X Peter Hasselblatt http://orcid.org/0000-0002-1107-6516 Patrick Stoll http://orcid.org/0000-0001-8133-2071 Lisa Fauth http://orcid.org/0000-0001-5183-7140 Manfred W Baumstark http://orcid.org/0000-0002-5442-1586 Irmgard Merfort http://orcid.org/0000-0003-4716-5016 Annette Schmitt-Graeff http://orcid.org/0000-0001-5082-7979 Wolfgang Kreisel http://orcid.org/0000-0001-6884-0135
Funding Agency and Grant Number
Corresponding Author	Wolfgang Kreisel, MD, Emeritus Professor, Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, Freiburg 79106, Germany. wolfgang.kreisel@uniklinik-freiburg.de
Key Words	Portal hypertension; Thioacetamide; Nitric oxide; Liver cirrhosis; Cyclic guanosine monophosphate; Phosphodiesterase-5; Sildenafil; Hepatic stellate cells; Metabolic zonation
Core Tip	A constriction of sinusoids plays an im­portant role in the pathogenesis of cirrhotic portal hypertension, wherein the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway plays a pivotal role. In a rat model of liver cirrhosis phosphodiesterase-5 (PDE-5) was markedly overexpressed both on the mRNA and the protein level. PDE-5 converts the vasodilating cGMP to inactive 5’-GMP. In healthy liver a zonation of PDE-5 was found which is abrogated in cirrhosis. Serum cGMP was reduced in cirrhosis. Inhibition of PDE-5 by Sildenafil normalized serum cGMP levels and lowered portal venous pressure. Hence, the inhibition of PDE-5 may be a promising adjunct in portal hypertension therapy.
Publish Date	2018-10-12 05:32
Citation	Schaffner D, Lazaro A, Deibert P, Hasselblatt P, Stoll P, Fauth L, Baumstark MW, Merfort I, Schmitt-Graeff A, Kreisel W. Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension. World J Gastroenterol 2018; 24(38): 4356-4368
URL	http://www.wjgnet.com/1007-9327/full/v24/i38/4356.htm
DOI	http://dx.doi.org/10.3748/wjg.v24.i38.4356

Full Article (PDF)	WJG-24-4356.pdf
The ARRIVE Guidelines	40791-The ARRIVE guidelines.pdf
Manuscript File	40791-Review.docx
Answering Reviewers	40791-Answering reviewers.pdf
Audio Core Tip	40791-Audio core tip.MOV
Biostatistics Review Certificate	40791-Biostatistics statement.pdf
Conflict-of-Interest Disclosure Form	40791-Conflict-of-interest statement.pdf
Copyright License Agreement	40791-Copyright license agreement.pdf
Institutional Animal Care and Use Committee Approval Form or Document	40791-Institutional animal care and use committee statement.pdf
Institutional Review Board Approval Form or Document	40791-Institutional-Review-Board-Approval-Form-or-Document-revision.pdf
Non-Native Speakers of English Editing Certificate	40791-Language certificate.pdf
Video	40791-Video-revision.docx
Supplementary Material	40791-Supplementary-Material-revision.docx
Peer-review Report	40791-Peer-review(s).pdf
Scientific Misconduct Check	40791-Scientific misconduct check.pdf
Scientific Editor Work List	40791-Scientific editor work list.pdf