{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T21:01:24Z","timestamp":1774040484431,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NETHERLANDS CARDIOVASCULAR RESEARCH INITIATIVE (CVON): the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences","award":["CVON Phaedra 2012-08"],"award-info":[{"award-number":["CVON Phaedra 2012-08"]}]},{"name":"NETHERLANDS CARDIOVASCULAR RESEARCH INITIATIVE (CVON): the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences","award":["917.16.446"],"award-info":[{"award-number":["917.16.446"]}]},{"DOI":"10.13039\/501100003246","name":"NETHERLANDS ORGANIZATION FOR SCIENTIFIC RESEARCH (NWO) and the NETHERLANDS ORGANIZATION FOR HEALTH RESEARCH AND DEVELOPMENT","doi-asserted-by":"publisher","award":["CVON Phaedra 2012-08"],"award-info":[{"award-number":["CVON Phaedra 2012-08"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"NETHERLANDS ORGANIZATION FOR SCIENTIFIC RESEARCH (NWO) and the NETHERLANDS ORGANIZATION FOR HEALTH RESEARCH AND DEVELOPMENT","doi-asserted-by":"publisher","award":["917.16.446"],"award-info":[{"award-number":["917.16.446"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) is a rare, progressive, and incurable disease characterized by an elevated pulmonary blood pressure, extensive remodeling of the pulmonary vasculature, increased pulmonary vascular resistance, and culminating in right ventricular failure. Mitochondrial dysfunction has a major role in the pathogenesis of PAH and secondary right ventricular failure, and its targeting may offer therapeutic benefit. In this study, we provide proof-of-concept for the use of the mitochondrially active drug SUL-150 to treat PAH. PAH was induced in rats by monocrotaline, followed by the placement of an aortocaval shunt one week later. The mitoprotective compound SUL-150 (~6 mg\u00b7kg\u22121\u00b7day\u22121) or vehicle was administered intraperitoneally via osmotic minipump for 28 days, implanted at the time of aortocaval shunt placement. Vehicle-treated PAH rats had dyspnea and showed pulmonary artery remodeling with increased responsiveness to phenylephrine, in addition to remodeling of the intrapulmonary arterioles. SUL-150 administration mitigated the dyspnea and the remodeling responses. Vehicle-treated PAH rats developed right ventricular hypertrophy, fibrosis, and failure. SUL-150 administration precluded cardiomyocyte hypertrophy and inhibited ventricular fibrogenesis. Right ventricular failure in vehicle-treated PAH rats induced mitochondrial loss and dysfunction associated with a decrease in mitophagy. SUL-150 was unable to prevent the mitochondrial loss but improved mitochondrial health in the right ventricle, which culminated in the preservation of right ventricular function. We conclude that SUL-150 improves PAH-associated morbidity by the amelioration of pulmonary vascular remodeling and right ventricular failure and may be considered a promising therapeutic candidate to slow disease progression in pulmonary arterial hypertension and secondary right ventricular failure.<\/jats:p>","DOI":"10.3390\/ijms26157181","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T09:35:11Z","timestamp":1753436111000},"page":"7181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SUL-150 Limits Vascular Remodeling and Ventricular Failure in Pulmonary Arterial Hypertension"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3511-1988","authenticated-orcid":false,"given":"Lysanne M.","family":"Jorna","sequence":"first","affiliation":[{"name":"Department of Pediatric and Congenital Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (CA40), 9713 GZ Groningen, The Netherlands"},{"name":"Laboratory for Cardiovascular Regenerative Medicine, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0900-0130","authenticated-orcid":false,"given":"Dalibor","family":"Nakl\u00e1dal","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (AP50), 9713 GZ Groningen, The Netherlands"},{"name":"Clinical Research Unit, Comenius University Science Park, Comenius University Bratislava, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes N.","family":"van Heuveln","sequence":"additional","affiliation":[{"name":"Department of Experimental Pharmacology, Medical Faculty Mannheim, University of Heidelberg, Ludolf Krehlstrasse 13-17, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diederik E.","family":"van der Feen","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Congenital Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (CA40), 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quint A. J.","family":"Hagdorn","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Congenital Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (CA40), 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido P. L.","family":"Bossers","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Congenital Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (CA40), 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemieke","family":"van Oosten","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Congenital Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (CA40), 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Weij","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Congenital Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (CA40), 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludmila","family":"Tk\u00e1\u010dikov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Veterinary Medicine and Pharmacy, Komensk\u00e9ho 73, 041 81 Ko\u0161ice, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4457-7541","authenticated-orcid":false,"given":"So\u0148a","family":"Tk\u00e1\u010dikov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Biophysics, Faculty of Medicine, Pavol Jozef \u0160af\u00e1rik University, Trieda SNP 1, 040 11 Ko\u0161ice, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5135-4621","authenticated-orcid":false,"given":"Robert H.","family":"Henning","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (AP50), 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7128-2741","authenticated-orcid":false,"given":"Martin C.","family":"Harmsen","sequence":"additional","affiliation":[{"name":"Laboratory for Cardiovascular Regenerative Medicine, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4385-5784","authenticated-orcid":false,"given":"Rolf M. F.","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Congenital Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (CA40), 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5850-5667","authenticated-orcid":false,"given":"Guido","family":"Krenning","sequence":"additional","affiliation":[{"name":"Laboratory for Cardiovascular Regenerative Medicine, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713 GZ Groningen, The Netherlands"},{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (AP50), 9713 GZ Groningen, The Netherlands"},{"name":"Sulfateq B.V., Admiraal de Ruyterlaan 5, 9726 GN Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s00109-013-0998-0","article-title":"Vascular remodeling in pulmonary hypertension","volume":"91","author":"Shimoda","year":"2013","journal-title":"J. Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/S2213-2600(15)00543-3","article-title":"A global view of pulmonary hypertension","volume":"4","author":"Hoeper","year":"2016","journal-title":"Lancet. Respir. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1378\/chest.15-0300","article-title":"Five-Year outcomes of patients enrolled in the REVEAL Registry","volume":"148","author":"Farber","year":"2015","journal-title":"Chest"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1700740","DOI":"10.1183\/13993003.00740-2017","article-title":"Mortality in pulmonary arterial hypertension: Prediction by the 2015 European pulmonary hypertension guidelines risk stratification model","volume":"50","author":"Hoeper","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1056\/NEJMra040291","article-title":"Treatment of pulmonary arterial hypertension","volume":"351","author":"Humbert","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"191","DOI":"10.4065\/84.2.191","article-title":"Pulmonary hypertension: Diagnosis and management","volume":"84","author":"McGoon","year":"2009","journal-title":"Mayo Clin. Proc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1161\/CIRCHEARTFAILURE.111.966127","article-title":"Metabolic gene remodeling and mitochondrial dysfunction in failing right ventricular hypertrophy secondary to pulmonary arterial hypertension","volume":"6","author":"Mizuno","year":"2013","journal-title":"Circ. Heart Fail."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12931-015-0178-6","article-title":"Increased in vivo mitochondrial oxygenation with right ventricular failure induced by pulmonary arterial hypertension: Mitochondrial inhibition as driver of cardiac failure?","volume":"16","author":"Balestra","year":"2015","journal-title":"Respir. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"L782","DOI":"10.1152\/ajplung.00331.2017","article-title":"Mitochondrial dysfunction and pulmonary hypertension: Cause, effect, or both","volume":"314","author":"Marshall","year":"2018","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_10","unstructured":"Wang, Y.-X. (2017). Mitochondrial and Metabolic Drivers of Pulmonary Vascular Endothelial Dysfunction in Pulmonary Hypertension. Pulmonary Vasculature Redox Signaling in Health and Disease, Springer International Publishing."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1161\/CIRCULATIONAHA.114.006979","article-title":"Emerging concepts in the molecular basis of pulmonary arterial hypertension: Part I: Metabolic plasticity and mitochondrial dynamics in the pulmonary circulation and right ventricle in pulmonary arterial hypertension","volume":"131","author":"Ryan","year":"2015","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.cmet.2014.08.011","article-title":"Sirtuin 3 deficiency is associated with inhibited mitochondrial function and pulmonary arterial hypertension in rodents and humans","volume":"20","author":"Paulin","year":"2014","journal-title":"Cell Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"eaao4583","DOI":"10.1126\/scitranslmed.aao4583","article-title":"Inhibition of pyruvate dehydrogenase kinase improves pulmonary arterial hypertension in genetically susceptible patients","volume":"9","author":"Michelakis","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.redox.2014.06.010","article-title":"Coenzyme Q supplementation in pulmonary arterial hypertension","volume":"2","author":"Sharp","year":"2014","journal-title":"Redox Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.biomaterials.2016.12.008","article-title":"The 6-chromanol derivate SUL-109 enables prolonged hypothermic storage of adipose tissue-derived stem cells","volume":"119","author":"Hajmousa","year":"2017","journal-title":"Biomaterials"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1093\/ndt\/gfy080","article-title":"The 6-hydroxychromanol derivative SUL-109 ameliorates renal injury after deep hypothermia and rewarming in rats","volume":"33","author":"Vogelaar","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Han, B., Poppinga, W.J., Zuo, H., Zuidhof, A.B., Bos, I.S., Smit, M., Vogelaar, P., Krenning, G., Henning, R.H., and Maarsingh, H. (2016). The novel compound Sul-121 inhibits airway inflammation and hyperresponsiveness in experimental models of chronic obstructive pulmonary disease. Sci. Rep., 6.","DOI":"10.1038\/srep26928"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lambooy, S.P.H., Bidadkosh, A., Nakladal, D., van Buiten, A., Girgis, R.A.T., van der Graaf, A.C., Wiedenmann, T.J., Koster, R.A., Vogelaar, P., and Buikema, H. (2017). The Novel Compound Sul-121 Preserves Endothelial Function and Inhibits Progression of Kidney Damage in Type 2 Diabetes Mellitus in Mice. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-11582-6"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nakladal, D., Buikema, H., Romero, A.R., Lambooy, S.P.H., Bouma, J., Krenning, G., Vogelaar, P., van der Graaf, A.C., Groves, M.R., and Kyselovic, J. (2019). The (R)-enantiomer of the 6-chromanol derivate SUL-121 improves renal graft perfusion via antagonism of the alpha1-adrenoceptor. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-36788-0"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.carpath.2015.09.009","article-title":"Impaired mitochondrial biogenesis is a common feature to myocardial hypertrophy and end-stage ischemic heart failure","volume":"25","author":"Pisano","year":"2016","journal-title":"Cardiovasc. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s00109-015-1254-6","article-title":"Mitophagy and heart failure","volume":"93","author":"Shires","year":"2015","journal-title":"J. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.biocel.2017.05.001","article-title":"Norepinephrine stimulation of alpha1D-adrenoceptor promotes proliferation of pulmonary artery smooth muscle cells via ERK-1\/2 signaling","volume":"88","author":"Liu","year":"2017","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1161\/01.RES.0000145360.16770.9f","article-title":"Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis","volume":"95","author":"McMurtry","year":"2004","journal-title":"Circ. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s00441-016-2539-y","article-title":"Pulmonary vascular remodeling in pulmonary hypertension","volume":"367","author":"Tuder","year":"2017","journal-title":"Cell Tissue Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Da Cruz, E.M., Ivy, D., and Jaggers, J. (2014). Animal Models for PAH and Increased Pulmonary Blood Flow. Pediatric and Congenital Cardiology, Cardiac Surgery and Intensive Care, Springer London.","DOI":"10.1007\/978-1-4471-4619-3"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1161\/01.RES.0000261658.12024.18","article-title":"Rho kinase-mediated vasoconstriction is important in severe occlusive pulmonary arterial hypertension in rats","volume":"100","author":"Oka","year":"2007","journal-title":"Circ. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1097\/RTI.0b013e3181ced14d","article-title":"Correlation of a scintigraphic pulmonary perfusion index with hemodynamic parameters in patients with pulmonary arterial hypertension","volume":"25","author":"Talwar","year":"2010","journal-title":"J. Thorac. Imaging"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1164\/ajrccm.157.5.9709050","article-title":"Pulmonary artery remodeling differs in hypoxia- and monocrotaline-induced pulmonary hypertension","volume":"157","author":"Smits","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.healun.2007.06.008","article-title":"Assessment of pulmonary vascular resistance by Doppler echocardiography in patients with pulmonary arterial hypertension","volume":"26","author":"Selimovic","year":"2007","journal-title":"J. Heart Lung Transplant."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s00109-010-0670-x","article-title":"The role of mitochondria in pulmonary vascular remodeling","volume":"88","author":"Dromparis","year":"2010","journal-title":"J. Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1023\/A:1006876031121","article-title":"Human myocardial ATP content and in vivo contractile function","volume":"180","author":"Starling","year":"1998","journal-title":"Mol. Cell Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1378\/chest.06-1263","article-title":"Right ventricular diastolic dysfunction and the acute effects of sildenafil in pulmonary hypertension patients","volume":"132","author":"Gan","year":"2007","journal-title":"Chest"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tian, L., Potus, F., Wu, D., Dasgupta, A., Chen, K.H., Mewburn, J., Lima, P., and Archer, S.L. (2018). Increased Drp1-Mediated Mitochondrial Fission Promotes Proliferation and Collagen Production by Right Ventricular Fibroblasts in Experimental Pulmonary Arterial Hypertension. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00828"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Power, A.S., Norman, R., Jones, T.L.M., Hickey, A.J., and Ward, M.L. (2019). Mitochondrial function remains impaired in the hypertrophied right ventricle of pulmonary hypertensive rats following short duration metoprolol treatment. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0214740"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1042\/bse0470069","article-title":"Regulation of mitochondrial biogenesis","volume":"47","author":"Jornayvaz","year":"2010","journal-title":"Essays Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4892","DOI":"10.1111\/jcmm.15194","article-title":"Mitochondrial biogenesis: An update","volume":"24","author":"Popov","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.freeradbiomed.2016.04.015","article-title":"Mechanisms of mitophagy: PINK1, Parkin, USP30 and beyond","volume":"100","author":"Bingol","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.tcb.2016.05.008","article-title":"Deciphering the Molecular Signals of PINK1\/Parkin Mitophagy","volume":"26","author":"Nguyen","year":"2016","journal-title":"Trends Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11010-012-1485-6","article-title":"Skeletal muscle mitochondrial dysfunction precedes right ventricular impairment in experimental pulmonary hypertension","volume":"373","author":"Enache","year":"2013","journal-title":"Mol. Cell. Biochem."},{"key":"ref_40","first-page":"5655","article-title":"Qiliqiangxin prevents right ventricular remodeling by inhibiting apoptosis and improving metabolism reprogramming with pulmonary arterial hypertension","volume":"12","author":"Lu","year":"2020","journal-title":"Am. J. Transl. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s00109-015-1263-5","article-title":"Mitochondrial dynamics in pulmonary arterial hypertension","volume":"93","author":"Ryan","year":"2015","journal-title":"J. Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"L1","DOI":"10.1152\/ajplung.00031.2013","article-title":"The role of disturbed blood flow in the development of pulmonary arterial hypertension: Lessons from preclinical animal models","volume":"305","author":"Dickinson","year":"2013","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1164\/rccm.201103-0412OC","article-title":"A novel murine model of severe pulmonary arterial hypertension","volume":"184","author":"Ciuclan","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"L363","DOI":"10.1152\/ajplung.00212.2011","article-title":"The monocrotaline model of pulmonary hypertension in perspective","volume":"302","author":"Farkas","year":"2012","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1097\/00000542-200312000-00027","article-title":"Pulmonary arterial hypertension: Pathophysiology and anesthetic approach","volume":"99","author":"Blaise","year":"2003","journal-title":"Anesthesiology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/1465-9921-15-65","article-title":"N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats","volume":"15","author":"Chaumais","year":"2014","journal-title":"Respir. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/S0735-1097(03)00555-2","article-title":"Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension","volume":"42","author":"Ghofrani","year":"2003","journal-title":"J. Am. Col. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e13157","DOI":"10.14814\/phy2.13157","article-title":"Estrogen maintains mitochondrial content and function in the right ventricle of rats with pulmonary hypertension","volume":"5","author":"Liu","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1164\/rccm.201003-0335OC","article-title":"Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats","volume":"182","author":"Bogaard","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"H2316","DOI":"10.1152\/ajpheart.00792.2006","article-title":"Alpha1-adrenoceptor-dependent vascular hypertrophy and remodeling in murine hypoxic pulmonary hypertension","volume":"292","author":"Faber","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0002-9343(81)90261-8","article-title":"Improved right ventricular function and reduced pulmonary vascular resistance during prazosin therapy of congestive heart failure","volume":"71","author":"Colucci","year":"1981","journal-title":"Am. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1086\/679724","article-title":"The sexual dimorphism associated with pulmonary hypertension corresponds to a fibrotic phenotype","volume":"5","author":"Rafikova","year":"2015","journal-title":"Pulm. Circ."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.healun.2024.02.004","article-title":"Investigating the \u201csex paradox\u201d in pulmonary arterial hypertension: Results from the Pulmonary Hypertension Association Registry (PHAR)","volume":"43","author":"DesJardin","year":"2024","journal-title":"J. Heart Lung Transplant."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1183\/09031936.05.00015405","article-title":"The role of increased pulmonary blood flow in pulmonary arterial hypertension","volume":"26","author":"Schoemaker","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1093\/cvr\/24.5.430","article-title":"Simple, rapid, and effective method of producing aortocaval shunts in the rat","volume":"24","author":"Garcia","year":"1990","journal-title":"Cardiovasc. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1159\/000123059","article-title":"Artificial induction of melatonin rhythms by programmed microinfusion","volume":"31","author":"Lynch","year":"1980","journal-title":"Neuroendocrinology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1538\/expanim.52.285","article-title":"Progressive development of pulmonary hypertension leading to right ventricular hypertrophy assessed by echocardiography in rats","volume":"52","author":"Kato","year":"2003","journal-title":"Exp. Anim."},{"key":"ref_58","first-page":"H818","article-title":"Rat pulmonary circulation after chronic hypoxia: Hemodynamic and structural features","volume":"236","author":"Rabinovitch","year":"1979","journal-title":"Am. J. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ddmod.2011.04.001","article-title":"Tension Measurement in Isolated Rat and Mouse Pulmonary Artery","volume":"7","author":"Ko","year":"2010","journal-title":"Drug Discov. Today Dis. Model."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_61","first-page":"55065","article-title":"Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension","volume":"120","author":"Weij","year":"2017","journal-title":"J. Vis. Exp. JoVE"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S0891-5849(98)00315-3","article-title":"Antioxidant activity applying an improved ABTS radical cation decolorization assay","volume":"26","author":"Re","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.yjmcc.2012.04.015","article-title":"A novel player in cellular hypertrophy: Gibetagamma\/PI3K-dependent activation of the RacGEF TIAM-1 is required for alpha(1)-adrenoceptor induced hypertrophy in neonatal rat cardiomyocytes","volume":"53","author":"Vettel","year":"2012","journal-title":"J. Mol. Cell. Cardiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7181\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:15:51Z","timestamp":1760033751000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,25]]},"references-count":64,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26157181"],"URL":"https:\/\/doi.org\/10.3390\/ijms26157181","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,25]]}}}