{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T20:17:21Z","timestamp":1757621841923,"version":"3.44.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T00:00:00Z","timestamp":1754697600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T00:00:00Z","timestamp":1754697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Scientific Research Projects Foundation of Inonu University","award":["TDK-2017-739"],"award-info":[{"award-number":["TDK-2017-739"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cardiovasc Disord"],"DOI":"10.1186\/s12872-025-05065-0","type":"journal-article","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T05:11:27Z","timestamp":1754716287000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of cilomilast, tadalafil, and both drug combinations in the treatment of monocrotaline-induced pulmonary arterial hypertension in rats"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6781-7478","authenticated-orcid":false,"given":"Necip","family":"Ermis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9018-7849","authenticated-orcid":false,"given":"Onural","family":"Ozhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5686-7867","authenticated-orcid":false,"given":"Azibe","family":"Y\u0131ld\u0131z","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5072-2031","authenticated-orcid":false,"given":"Zeynep","family":"Ulutas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9497-3468","authenticated-orcid":false,"given":"Hakan","family":"Parlakpinar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4447-6233","authenticated-orcid":false,"given":"Ahmet","family":"Ulu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6080-229X","authenticated-orcid":false,"given":"Burhan","family":"Ates","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0576-1696","authenticated-orcid":false,"given":"Nigar","family":"Vardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7956-9272","authenticated-orcid":false,"given":"Zeynep","family":"Kucukakcali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1131-1878","authenticated-orcid":false,"given":"Ahmet","family":"Acet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,9]]},"reference":[{"key":"5065_CR1","doi-asserted-by":"crossref","unstructured":"Humbert M, Guignabert C, Bonnet S, Dorfm\u00fcller P, Klinger JR, Nicolls MR, Olschewski AJ, Pullamsetti SS, Schermuly RT, Stenmark KR et al. Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives. Eur Respir J. 2019;53(1):1801887.","DOI":"10.1183\/13993003.01887-2018"},{"issue":"6","key":"5065_CR2","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1378\/chest.14-1678","volume":"147","author":"A Hautefort","year":"2015","unstructured":"Hautefort A, Girerd B, Montani D, Cohen-Kaminsky S, Price L, Lambrecht BN, Humbert M, Perros F. T-helper 17 cell polarization in pulmonary arterial hypertension. Chest. 2015;147(6):1610\u201320.","journal-title":"Chest"},{"issue":"3","key":"5065_CR3","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1164\/rccm.201201-0164OC","volume":"186","author":"E Stacher","year":"2012","unstructured":"Stacher E, Graham BB, Hunt JM, Gandjeva A, Groshong SD, McLaughlin VV, Jessup M, Grizzle WE, Aldred MA, Cool CD, et al. Modern age pathology of pulmonary arterial hypertension. Am J Respir Crit Care Med. 2012;186(3):261\u201372.","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"5065_CR4","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1161\/CIRCRESAHA.113.301141","volume":"115","author":"M Rabinovitch","year":"2014","unstructured":"Rabinovitch M, Guignabert C, Humbert M, Nicolls MR. Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension. Circul Res. 2014;115(1):165\u201375.","journal-title":"Circul Res"},{"issue":"8","key":"5065_CR5","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1161\/CIRCRESAHA.110.236927","volume":"109","author":"R Tamosiuniene","year":"2011","unstructured":"Tamosiuniene R, Tian W, Dhillon G, Wang L, Sung YK, Gera L, Patterson AJ, Agrawal R, Rabinovitch M, Ambler K, et al. Regulatory T cells limit vascular endothelial injury and prevent pulmonary hypertension. Circul Res. 2011;109(8):867\u201379.","journal-title":"Circul Res"},{"issue":"2","key":"5065_CR6","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1002\/med.20020","volume":"25","author":"A Castro","year":"2005","unstructured":"Castro A, Jerez MJ, Gil C, Martinez A. Cyclic nucleotide phosphodiesterases and their role in Immunomodulatory responses: advances in the development of specific phosphodiesterase inhibitors. Med Res Rev. 2005;25(2):229\u201344.","journal-title":"Med Res Rev"},{"issue":"9","key":"5065_CR7","first-page":"Cd002309","volume":"9","author":"J Chong","year":"2017","unstructured":"Chong J, Leung B, Poole P. Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017;9(9):Cd002309.","journal-title":"Cochrane Database Syst Rev"},{"issue":"28","key":"5065_CR8","doi-asserted-by":"publisher","first-page":"3054","DOI":"10.2174\/0929867324666170530093902","volume":"24","author":"LI Sakkas","year":"2017","unstructured":"Sakkas LI, Mavropoulos A, Bogdanos DP. Phosphodiesterase 4 inhibitors in Immune-mediated diseases: mode of action, clinical applications, current and future perspectives. Curr Med Chem. 2017;24(28):3054\u201367.","journal-title":"Curr Med Chem"},{"issue":"12","key":"5065_CR9","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1136\/thx.2006.075937","volume":"62","author":"DC Grootendorst","year":"2007","unstructured":"Grootendorst DC, Gauw SA, Verhoosel RM, Sterk PJ, Hospers JJ, Bredenbr\u00f6ker D, Bethke TD, Hiemstra PS, Rabe KF. Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor Roflumilast in patients with COPD. Thorax. 2007;62(12):1081\u20137.","journal-title":"Thorax"},{"issue":"1","key":"5065_CR10","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/S0022-3565(24)29537-9","volume":"297","author":"A Hatzelmann","year":"2001","unstructured":"Hatzelmann A, Schudt C. Anti-inflammatory and Immunomodulatory potential of the novel PDE4 inhibitor Roflumilast in vitro. J Pharmacol Exp Ther. 2001;297(1):267\u201379.","journal-title":"J Pharmacol Exp Ther"},{"issue":"2","key":"5065_CR11","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.pupt.2004.10.001","volume":"18","author":"NA Jones","year":"2005","unstructured":"Jones NA, Boswell-Smith V, Lever R, Page CP. The effect of selective phosphodiesterase isoenzyme Inhibition on neutrophil function in vitro. Pulm Pharmacol Ther. 2005;18(2):93\u2013101.","journal-title":"Pulm Pharmacol Ther"},{"issue":"1","key":"5065_CR12","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.ejphar.2011.02.042","volume":"659","author":"S Kubo","year":"2011","unstructured":"Kubo S, Kobayashi M, Iwata M, Takahashi K, Miyata K, Shimizu Y. Disease-modifying effect of ASP3258, a novel phosphodiesterase type 4 inhibitor, on subchronic cigarette smoke exposure-induced lung injury in guinea pigs. Eur J Pharmacol. 2011;659(1):79\u201384.","journal-title":"Eur J Pharmacol"},{"issue":"8","key":"5065_CR13","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.1002\/jcp.22529","volume":"226","author":"J Selige","year":"2011","unstructured":"Selige J, Hatzelmann A, Dunkern T. The differential impact of PDE4 subtypes in human lung fibroblasts on cytokine-induced proliferation and myofibroblast conversion. J Cell Physiol. 2011;226(8):1970\u201380.","journal-title":"J Cell Physiol"},{"issue":"1\u20133","key":"5065_CR14","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.ejphar.2013.02.049","volume":"706","author":"JW Park","year":"2013","unstructured":"Park JW, Ryter SW, Kyung SY, Lee SP, Jeong SH. The phosphodiesterase 4 inhibitor rolipram protects against cigarette smoke extract-induced apoptosis in human lung fibroblasts. Eur J Pharmacol. 2013;706(1\u20133):76\u201383.","journal-title":"Eur J Pharmacol"},{"issue":"2","key":"5065_CR15","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1159\/000024001","volume":"117","author":"T Momose","year":"1998","unstructured":"Momose T, Okubo Y, Horie S, Suzuki J, Isobe M, Sekiguchi M. Effects of intracellular Cyclic AMP modulators on human eosinophil survival, degranulation and CD11b expression. Int Arch Allergy Immunol. 1998;117(2):138\u201345.","journal-title":"Int Arch Allergy Immunol"},{"issue":"2","key":"5065_CR16","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.neuroscience.2005.06.029","volume":"135","author":"JH McLean","year":"2005","unstructured":"McLean JH, Darby-King A, Harley CW. Potentiation and prolongation of long-term odor memory in neonate rats using a phosphodiesterase inhibitor. Neuroscience. 2005;135(2):329\u201334.","journal-title":"Neuroscience"},{"issue":"6","key":"5065_CR17","doi-asserted-by":"publisher","first-page":"374","DOI":"10.3109\/14017431.2012.729272","volume":"46","author":"WH Zhang","year":"2012","unstructured":"Zhang WH, Liu CP, Zhang YJ, Ji YQ, Lu WX, Zeng Q. Additive effect of Tadalafil and Simvastatin on monocrotaline-induced pulmonary hypertension rats. Scandinavian Cardiovasc Journal: SCJ. 2012;46(6):374\u201380.","journal-title":"Scandinavian Cardiovasc Journal: SCJ"},{"key":"5065_CR18","doi-asserted-by":"crossref","unstructured":"Ma Z, Mao L, Rajagopal S. Hemodynamic characterization of rodent models of pulmonary arterial hypertension. J Vis Exp JoVE. 2016(110):53335.","DOI":"10.3791\/53335"},{"issue":"1","key":"5065_CR19","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/1465-9921-7-9","volume":"7","author":"EJ Growcott","year":"2006","unstructured":"Growcott EJ, Spink KG, Ren X, Afzal S, Banner KH, Wharton J. Phosphodiesterase type 4 expression and anti-proliferative effects in human pulmonary artery smooth muscle cells. Respir Res. 2006;7(1):9.","journal-title":"Respir Res"},{"issue":"12","key":"5065_CR20","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1093\/ehjci\/jex244","volume":"18","author":"M Galderisi","year":"2017","unstructured":"Galderisi M, Cosyns B, Edvardsen T, Cardim N, Delgado V, Di Salvo G, Donal E, Sade LE, Ernande L, Garbi M, et al. Standardization of adult transthoracic echocardiography reporting in agreement with recent chamber quantification, diastolic function, and heart valve disease recommendations: an expert consensus document of the European association of cardiovascular imaging. Eur Heart J Cardiovasc Imaging. 2017;18(12):1301\u201310.","journal-title":"Eur Heart J Cardiovasc Imaging"},{"issue":"6","key":"5065_CR21","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1111\/fcp.13033","volume":"38","author":"S Ayik","year":"2024","unstructured":"Ayik S, Gunata M, Ozhan O, Yildiz A, Vardi N, Sonmez E, Ermis N, Ates N, Kilic E, Noma SAA, et al. Alamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin. Fundam Clin Pharmacol. 2024;38(6):1143\u201354.","journal-title":"Fundam Clin Pharmacol"},{"key":"5065_CR22","doi-asserted-by":"crossref","unstructured":"Aebi H. Catalase. In: Bergmeyer HU, editor. Methods of enzymatic analysis (second edition). Academic Press; 1974. pp. 673\u2013684.","DOI":"10.1016\/B978-0-12-091302-2.50032-3"},{"issue":"22","key":"5065_CR23","doi-asserted-by":"publisher","first-page":"6049","DOI":"10.1016\/S0021-9258(18)63504-5","volume":"244","author":"JM McCord","year":"1969","unstructured":"McCord JM, Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969;244(22):6049\u201355.","journal-title":"J Biol Chem"},{"key":"5065_CR24","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/S0076-6879(81)77050-2","volume":"77","author":"TP Akerboom","year":"1981","unstructured":"Akerboom TP, Sies H. Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples. Methods Enzymol. 1981;77:373\u201382.","journal-title":"Methods Enzymol"},{"issue":"2","key":"5065_CR25","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/0003-2697(66)90167-9","volume":"16","author":"ZA Placer","year":"1966","unstructured":"Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem. 1966;16(2):359\u201364.","journal-title":"Anal Biochem"},{"key":"5065_CR26","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","volume":"72","author":"MM Bradford","year":"1976","unstructured":"Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248\u201354.","journal-title":"Anal Biochem"},{"key":"5065_CR27","doi-asserted-by":"crossref","unstructured":"Mansoor M, Ibrahim AF. Emerging mechanistic insights and therapeutic strategies for pulmonary arterial hypertension: a focus on right ventricular dysfunction and novel treatment pathways. Biomedicines. 2025;13(3):600.","DOI":"10.3390\/biomedicines13030600"},{"issue":"2","key":"5065_CR28","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1097\/CRD.0b013e3181cd612f","volume":"18","author":"R Mathew","year":"2010","unstructured":"Mathew R. Inflammation and pulmonary hypertension. Cardiol Rev. 2010;18(2):67\u201372.","journal-title":"Cardiol Rev"},{"issue":"4","key":"5065_CR29","doi-asserted-by":"publisher","first-page":"L363","DOI":"10.1152\/ajplung.00212.2011","volume":"302","author":"JG Gomez-Arroyo","year":"2012","unstructured":"Gomez-Arroyo JG, Farkas L, Alhussaini AA, Farkas D, Kraskauskas D, Voelkel NF, Bogaard HJ. The monocrotaline model of pulmonary hypertension in perspective. Am J Physiol Lung Cell Mol Physiol. 2012;302(4):L363\u2013369.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"3","key":"5065_CR30","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1161\/01.RES.0000111804.34509.94","volume":"94","author":"K Abe","year":"2004","unstructured":"Abe K, Shimokawa H, Morikawa K, Uwatoku T, Oi K, Matsumoto Y, Hattori T, Nakashima Y, Kaibuchi K, Sueishi K, et al. Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats. Circul Res. 2004;94(3):385\u201393.","journal-title":"Circul Res"},{"issue":"8","key":"5065_CR31","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1093\/cvr\/cvy284","volume":"115","author":"Y Kuwabara","year":"2019","unstructured":"Kuwabara Y, Tanaka-Ishikawa M, Abe K, Hirano M, Hirooka Y, Tsutsui H, Sunagawa K, Hirano K. Proteinase-activated receptor 1 antagonism ameliorates experimental pulmonary hypertension. Cardiovascular Res. 2019;115(8):1357\u201368.","journal-title":"Cardiovascular Res"},{"issue":"7","key":"5065_CR32","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1136\/thorax.58.7.573","volume":"58","author":"M Profita","year":"2003","unstructured":"Profita M, Chiappara G, Mirabella F, Di Giorgi R, Chimenti L, Costanzo G, Riccobono L, Bellia V, Bousquet J, Vignola AM. Effect of cilomilast (Ariflo) on TNF-alpha, IL-8, and GM-CSF release by airway cells of patients with COPD. Thorax. 2003;58(7):573\u20139.","journal-title":"Thorax"},{"issue":"8s","key":"5065_CR33","doi-asserted-by":"publisher","first-page":"S71","DOI":"10.1016\/j.amjcard.2017.06.012","volume":"120","author":"JR Klinger","year":"2017","unstructured":"Klinger JR, Kadowitz PJ. The nitric oxide pathway in pulmonary vascular disease. Am J Cardiol. 2017;120(8s):S71\u20139.","journal-title":"Am J Cardiol"},{"issue":"6","key":"5065_CR34","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/0922-4106(90)90031-R","volume":"189","author":"T Nakaki","year":"1990","unstructured":"Nakaki T, Nakayama M, Kato R. Inhibition by nitric oxide and nitric oxide-producing vasodilators of DNA synthesis in vascular smooth muscle cells. Eur J Pharmacol. 1990;189(6):347\u201353.","journal-title":"Eur J Pharmacol"},{"issue":"2","key":"5065_CR35","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1161\/01.RES.78.2.225","volume":"78","author":"R Sarkar","year":"1996","unstructured":"Sarkar R, Meinberg EG, Stanley JC, Gordon D, Webb RC. Nitric oxide reversibly inhibits the migration of cultured vascular smooth muscle cells. Circul Res. 1996;78(2):225\u201330.","journal-title":"Circul Res"},{"issue":"2","key":"5065_CR36","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1002\/j.2040-4603.2016.tb00688.x","volume":"6","author":"K Suresh","year":"2016","unstructured":"Suresh K, Shimoda LA. Lung circulation. Compr Physiol. 2016;6(2):897\u2013943.","journal-title":"Compr Physiol"},{"issue":"1","key":"5065_CR37","doi-asserted-by":"publisher","first-page":"L15","DOI":"10.1152\/ajplung.00322.2006","volume":"292","author":"RA Dweik","year":"2007","unstructured":"Dweik RA. The lung in the balance: arginine, methylated arginines, and nitric oxide. Am J Physiol Lung Cell Mol Physiol. 2007;292(1):L15\u201317.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"3","key":"5065_CR38","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1164\/ajrccm.158.3.9802066","volume":"158","author":"FT Kaneko","year":"1998","unstructured":"Kaneko FT, Arroliga AC, Dweik RA, Comhair SA, Laskowski D, Oppedisano R, Thomassen MJ, Erzurum SC. Biochemical reaction products of nitric oxide as quantitative markers of primary pulmonary hypertension. Am J Respir Crit Care Med. 1998;158(3):917\u201323.","journal-title":"Am J Respir Crit Care Med"},{"issue":"4","key":"5065_CR39","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1007\/s004080000064","volume":"179","author":"M Ozkan","year":"2001","unstructured":"Ozkan M, Dweik RA, Laskowski D, Arroliga AC, Erzurum SC. High levels of nitric oxide in individuals with pulmonary hypertension receiving Epoprostenol therapy. Lung. 2001;179(4):233\u201343.","journal-title":"Lung"},{"key":"5065_CR40","doi-asserted-by":"crossref","unstructured":"Lan NSH, Massam BD, Kulkarni SS, Lang CC. Pulmonary arterial hypertension: pathophysiology and treatment. Dis (Basel Switzerland). 2018;6(2):38.","DOI":"10.3390\/diseases6020038"},{"issue":"6","key":"5065_CR41","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1164\/ajrccm.159.6.9804054","volume":"159","author":"RM Tuder","year":"1999","unstructured":"Tuder RM, Cool CD, Geraci MW, Wang J, Abman SH, Wright L, Badesch D, Voelkel NF. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med. 1999;159(6):1925\u201332.","journal-title":"Am J Respir Crit Care Med"},{"issue":"3","key":"5065_CR42","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1002\/(SICI)1096-9896(199807)185:3<313::AID-PATH93>3.0.CO;2-8","volume":"185","author":"NA Mason","year":"1998","unstructured":"Mason NA, Springall DR, Burke M, Pollock J, Mikhail G, Yacoub MH, Polak JM. High expression of endothelial nitric oxide synthase in plexiform lesions of pulmonary hypertension. J Pathol. 1998;185(3):313\u20138.","journal-title":"J Pathol"},{"issue":"2","key":"5065_CR43","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/S0022-3565(24)37102-2","volume":"283","author":"MR Maclean","year":"1997","unstructured":"Maclean MR, Johnston ED, McCulloch KM, Pooley L, Houslay MD, Sweeney G. Phosphodiesterase isoforms in the pulmonary arterial circulation of the rat: changes in pulmonary hypertension. J Pharmacol Exp Ther. 1997;283(2):619\u201324.","journal-title":"J Pharmacol Exp Ther"},{"issue":"5 Pt 1","key":"5065_CR44","doi-asserted-by":"publisher","first-page":"C1405","DOI":"10.1152\/ajpcell.1994.267.5.C1405","volume":"267","author":"TL Cornwell","year":"1994","unstructured":"Cornwell TL, Arnold E, Boerth NJ, Lincoln TM. Inhibition of smooth muscle cell growth by nitric oxide and activation of cAMP-dependent protein kinase by cGMP. Am J Physiol. 1994;267(5 Pt 1):C1405\u20131413.","journal-title":"Am J Physiol"},{"key":"5065_CR45","doi-asserted-by":"crossref","unstructured":"Marsh LM, Jandl K, Gr\u00fcnig G, Foris V, Bashir M, Ghanim B, Klepetko W, Olschewski H, Olschewski A, Kwapiszewska G. The inflammatory cell landscape in the lungs of patients with idiopathic pulmonary arterial hypertension. Eur Respir J. 2018;51(1):1701214.","DOI":"10.1183\/13993003.01214-2017"},{"issue":"10","key":"5065_CR46","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1161\/ATVBAHA.116.307634","volume":"36","author":"L Aldabbous","year":"2016","unstructured":"Aldabbous L, Abdul-Salam V, McKinnon T, Duluc L, Pepke-Zaba J, Southwood M, Ainscough AJ, Hadinnapola C, Wilkins MR, Toshner M, et al. Neutrophil extracellular traps promote angiogenesis: evidence from vascular pathology in pulmonary hypertension. Arterioscler Thromb Vasc Biol. 2016;36(10):2078\u201387.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"5065_CR47","doi-asserted-by":"publisher","first-page":"14079","DOI":"10.1038\/ncomms14079","volume":"8","author":"LA Hurst","year":"2017","unstructured":"Hurst LA, Dunmore BJ, Long L, Crosby A, Al-Lamki R, Deighton J, Southwood M, Yang X, Nikolic MZ, Herrera B, et al. TNF\u03b1 drives pulmonary arterial hypertension by suppressing the BMP type-II receptor and altering NOTCH signalling. Nat Commun. 2017;8:14079.","journal-title":"Nat Commun"},{"issue":"8","key":"5065_CR48","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1164\/rccm.201402-0322OC","volume":"192","author":"M Le Hiress","year":"2015","unstructured":"Le Hiress M, Tu L, Ricard N, Phan C, Thuillet R, Fadel E, Dorfm\u00fcller P, Montani D, de Man F, Humbert M, et al. Proinflammatory signature of the dysfunctional endothelium in pulmonary hypertension. Role of the macrophage migration inhibitory Factor\/CD74 complex. Am J Respir Crit Care Med. 2015;192(8):983\u201397.","journal-title":"Am J Respir Crit Care Med"},{"issue":"6","key":"5065_CR49","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1096\/fj.07-098921","volume":"22","author":"L De Franceschi","year":"2008","unstructured":"De Franceschi L, Platt OS, Malpeli G, Janin A, Scarpa A, Leboeuf C, Beuzard Y, Payen E, Brugnara C. Protective effects of phosphodiesterase-4 (PDE-4) Inhibition in the early phase of pulmonary arterial hypertension in Transgenic sickle cell mice. FASEB Journal: Official Publication Federation Am Soc Experimental Biology. 2008;22(6):1849\u201360.","journal-title":"FASEB Journal: Official Publication Federation Am Soc Experimental Biology"},{"issue":"9","key":"5065_CR50","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1513\/AnnalsATS.201408-405CME","volume":"11","author":"MM Hayes","year":"2014","unstructured":"Hayes MM, Vedamurthy A, George G, Dweik R, Klings ES, Machado RF, Gladwin MT, Wilson KC, Thomson CC. Pulmonary hypertension in sickle cell disease. Annals Am Thorac Soc. 2014;11(9):1488\u20139.","journal-title":"Annals Am Thorac Soc"},{"issue":"1","key":"5065_CR51","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1124\/jpet.108.148742","volume":"330","author":"M Izikki","year":"2009","unstructured":"Izikki M, Raffestin B, Klar J, Hatzelmann A, Marx D, Tenor H, Zadigue P, Adnot S, Eddahibi S. Effects of roflumilast, a phosphodiesterase-4 inhibitor, on hypoxia- and monocrotaline-induced pulmonary hypertension in rats. J Pharmacol Exp Ther. 2009;330(1):54\u201362.","journal-title":"J Pharmacol Exp Ther"},{"issue":"3","key":"5065_CR52","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1007\/s11845-018-1738-9","volume":"187","author":"LF Shen","year":"2018","unstructured":"Shen LF, Lv XD, Chen WY, Yang Q, Fang ZX, Lu WF. Effect of Roflumilast on chronic obstructive pulmonary disease: a systematic review and meta-analysis. Ir J Med Sci. 2018;187(3):731\u20138.","journal-title":"Ir J Med Sci"},{"issue":"8","key":"5065_CR53","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1164\/rccm.200212-1490OC","volume":"168","author":"E Gamble","year":"2003","unstructured":"Gamble E, Grootendorst DC, Brightling CE, Troy S, Qiu Y, Zhu J, Parker D, Matin D, Majumdar S, Vignola AM, et al. Antiinflammatory effects of the phosphodiesterase-4 inhibitor cilomilast (Ariflo) in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;168(8):976\u201382.","journal-title":"Am J Respir Crit Care Med"},{"issue":"16","key":"5065_CR54","doi-asserted-by":"publisher","first-page":"7583","DOI":"10.1073\/pnas.91.16.7583","volume":"91","author":"SL Archer","year":"1994","unstructured":"Archer SL, Huang JM, Hampl V, Nelson DP, Shultz PJ, Weir EK. Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc Natl Acad Sci USA. 1994;91(16):7583\u20137.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"5065_CR55","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1161\/01.RES.0000087541.15600.2B","volume":"93","author":"SD Rybalkin","year":"2003","unstructured":"Rybalkin SD, Yan C, Bornfeldt KE, Beavo JA. Cyclic GMP phosphodiesterases and regulation of smooth muscle function. Circul Res. 2003;93(4):280\u201391.","journal-title":"Circul Res"},{"issue":"1","key":"5065_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1172\/JCI112536","volume":"78","author":"F Murad","year":"1986","unstructured":"Murad F. Cyclic Guanosine monophosphate as a mediator of vasodilation. J Clin Investig. 1986;78(1):1\u20135.","journal-title":"J Clin Investig"},{"issue":"Pt 10","key":"5065_CR57","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1242\/jcs.113.10.1671","volume":"113","author":"F Hofmann","year":"2000","unstructured":"Hofmann F, Ammendola A, Schlossmann J. Rising behind NO: cGMP-dependent protein kinases. J Cell Sci. 2000;113(Pt 10):1671\u20136.","journal-title":"J Cell Sci"},{"issue":"5444","key":"5065_CR58","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1126\/science.286.5444.1583","volume":"286","author":"HK Surks","year":"1999","unstructured":"Surks HK, Mochizuki N, Kasai Y, Georgescu SP, Tang KM, Ito M, Lincoln TM, Mendelsohn ME. Regulation of myosin phosphatase by a specific interaction with cGMP- dependent protein kinase ialpha. Sci (New York NY). 1999;286(5444):1583\u20137.","journal-title":"Sci (New York NY)"},{"issue":"6774","key":"5065_CR59","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/35004606","volume":"404","author":"J Schlossmann","year":"2000","unstructured":"Schlossmann J, Ammendola A, Ashman K, Zong X, Huber A, Neubauer G, Wang GX, Allescher HD, Korth M, Wilm M, et al. Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Ibeta. Nature. 2000;404(6774):197\u2013201.","journal-title":"Nature"},{"issue":"16","key":"5065_CR60","doi-asserted-by":"publisher","first-page":"10927","DOI":"10.1074\/jbc.274.16.10927","volume":"274","author":"M Fukao","year":"1999","unstructured":"Fukao M, Mason HS, Britton FC, Kenyon JL, Horowitz B, Keef KD. Cyclic GMP-dependent protein kinase activates cloned BKCa channels expressed in mammalian cells by direct phosphorylation at Serine 1072. J Biol Chem. 1999;274(16):10927\u201335.","journal-title":"J Biol Chem"},{"issue":"1","key":"5065_CR61","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1080\/07853890310004093","volume":"35","author":"J Schlossmann","year":"2003","unstructured":"Schlossmann J, Feil R, Hofmann F. Signaling through NO and cGMP-dependent protein kinases. Ann Med. 2003;35(1):21\u20137.","journal-title":"Ann Med"},{"key":"5065_CR62","doi-asserted-by":"publisher","first-page":"172777","DOI":"10.1016\/j.ejphar.2019.172777","volume":"865","author":"D Novelli","year":"2019","unstructured":"Novelli D, Fumagalli F, Staszewsky L, Ristagno G, Olivari D, Masson S, De Giorgio D, Ceriani S, Affatato R, De Logu F, et al. Monocrotaline-induced pulmonary arterial hypertension: Time-course of injury and comparative evaluation of Macitentan and Y-27632, a Rho kinase inhibitor. Eur J Pharmacol. 2019;865:172777.","journal-title":"Eur J Pharmacol"},{"key":"5065_CR63","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.ijcard.2018.12.078","volume":"283","author":"T Kramer","year":"2019","unstructured":"Kramer T, Dumitrescu D, Gerhardt F, Orlova K, Ten Freyhaus H, Hellmich M, Baldus S, Rosenkranz S. Therapeutic potential of phosphodiesterase type 5 inhibitors in heart failure with preserved ejection fraction and combined post- and pre-capillary pulmonary hypertension. Int J Cardiol. 2019;283:152\u20138.","journal-title":"Int J Cardiol"},{"issue":"12","key":"5065_CR64","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1001\/jama.2013.2024","volume":"309","author":"MM Redfield","year":"2013","unstructured":"Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, LeWinter MM, Rouleau JL, Bull DA, Mann DL, et al. Effect of phosphodiesterase-5 Inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013;309(12):1268\u201377.","journal-title":"JAMA"}],"container-title":["BMC Cardiovascular Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12872-025-05065-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12872-025-05065-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12872-025-05065-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T15:48:35Z","timestamp":1757346515000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccardiovascdisord.biomedcentral.com\/articles\/10.1186\/s12872-025-05065-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,9]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["5065"],"URL":"https:\/\/doi.org\/10.1186\/s12872-025-05065-0","relation":{},"ISSN":["1471-2261"],"issn-type":[{"type":"electronic","value":"1471-2261"}],"subject":[],"published":{"date-parts":[[2025,8,9]]},"assertion":[{"value":"9 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval was obtained from the Experimental Animal Ethics Board at \u0130n\u00f6n\u00fc University (2016\u00a0A-114).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"591"}}