{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:43:58Z","timestamp":1788414238198,"version":"build-2803163510"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T00:00:00Z","timestamp":1704672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Left heart disease (LHD) is the leading cause of pulmonary hypertension (PH). Its recent growth has not been matched by the design of therapeutic agents directly targeting the disease. Effective therapies approved for pulmonary arterial hypertension (PAH) have been shown to be inefficient in patients with PH-LHD. Hence, there is a need for an animal model that would closely mimic PH-LHD in preclinical experiments. The current study describes and compares a number of rodent models of left ventricular failure and their potential to induce PH. It also evaluates whether, and to what extent, common PH models could develop LV failure. Articles were identified in the Pubmed\/Medline and Web of Science online electronic databases following the PRISMA Protocol between 1992 and 2022. Quality assessment was carried out using the SYRCLE risk-of-bias tool for animal studies. Publication bias across studies using Egger\u2019s regression test statistic, was performed together with sensitivity analysis. A wide spectrum of protocols\u2013135 studies and 207 interventions, was examined, including systemic hypertensive models, pressure-overload-induced HF, model of ischemic heart failure, and metabolic approaches based on high fat diet or metabolic syndrome. The most pronounced alterations in PH-related parameters were demonstrated for the common PH models, but were also seen in animals with LV failure induced by ischemic conditions, pressure overload or metabolic conditions. Models based on aortic banding, transverse aortic constriction (TAC), or with myocardial infarction (MI) caused by coronary artery ligation, demonstrated more pronounced worsening in PH due to LV failure; however, they also demonstrated poor survival, especially the ischemic-HF model. Common PH models, excluding prolonged exposure to monocrotaline, do not promote LV hypertrophy. Prolonged exposure to a high-fat diet, or a two-hit model of an obese ZSF1 rat combined with SU5416-induced pulmonary endothelial impairment (a VEGF receptor antagonist) worsened PH and impaired diastolic dysfunction. Due to the limited number of protocols, further trials are needed to confirm the utility of such approaches for modeling PH in subjects with metabolic syndrome. This would provide a clearer insight into the complexity of LHD, PH and metabolic disorders in PH-LHD, and thus accelerate the development of new therapies in clinical trials.<\/jats:p>","DOI":"10.3389\/fphar.2023.1308095","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T05:16:25Z","timestamp":1704690985000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["An updated review of experimental rodent models of pulmonary hypertension and left heart disease"],"prefix":"10.3389","volume":"14","author":[{"given":"Magdalena","family":"Jasi\u0144ska-Stroschein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.ejps.2016.11.009","article-title":"Activation of GPER ameliorates experimental pulmonary hypertension in male rats","volume":"97","author":"Alencar","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"L924","DOI":"10.1152\/ajplung.00146.2015","article-title":"The pathophysiology of pulmonary hypertension in left heart disease","volume":"309","author":"Breitling","year":"2015","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/j.ejheart.2004.10.021","article-title":"Pulmonary vascular remodeling in pulmonary hypertension due to chronic heart failure","volume":"7","author":"Delgado","year":"2005","journal-title":"Eur. J. Heart Fail."},{"key":"B4","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1161\/CIRCHEARTFAILURE.111.964494","article-title":"Bisoprolol delays progression towards right heart failure in experimental pulmonary hypertension","volume":"5","author":"de Man","year":"2012","journal-title":"Circ. Heart Fail."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.1016\/j.jtcvs.2017.06.053","article-title":"Pulmonary hypertension due to left heart disease causes intrapulmonary venous arterialization in rats","volume":"154","author":"Fujimoto","year":"2017","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1136\/heartjnl-2021-319605","article-title":"Heart failure with preserved ejection fraction: recent concepts in diagnosis, mechanisms and management","volume":"108","author":"Gevaert","year":"2022","journal-title":"Heart"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1016\/j.jacc.2017.01.051","article-title":"Pulmonary hypertension in heart failure: pathophysiology, pathobiology, and emerging clinical perspectives","volume":"69","author":"Guazzi","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"B8","doi-asserted-by":"publisher","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":"B9","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1186\/s12967-020-02440-7","article-title":"Changes in heart morphometric parameters over the course of a monocrotaline-induced pulmonary arterial hypertension rat model","volume":"18","author":"Ho\u0142da","year":"2020","journal-title":"J. Transl. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/1471-2288-14-43","article-title":"SYRCLE's risk of bias tool for animal studies","volume":"14","author":"Hooijmans","year":"2014","journal-title":"BMC Med. Res. Methodol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2200879","DOI":"10.1183\/13993003.00879-2022","article-title":"ESC\/ERS Scientific Document Group. 2022 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"61","author":"Humbert","year":"2023","journal-title":"Eur. Respir. J."},{"key":"B12","doi-asserted-by":"publisher","first-page":"113251","DOI":"10.1016\/j.biopha.2022.113251","article-title":"Searching for an experimental rodent model of heart failure with preserved ejection fraction: Re-visited","volume":"152","author":"Jasi\u0144ska-Stroschein","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"B13","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.jjcc.2022.10.003","article-title":"Tofogliflozin, a sodium-glucose cotransporter 2 inhibitor, improves pulmonary vascular remodeling due to left heart disease in mice","author":"Joki","year":"2022","journal-title":"J. Cardiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"H507","DOI":"10.1152\/ajpheart.00862.2005","article-title":"Alveolar hypoxia induces left ventricular diastolic dysfunction and reduces phosphorylation of phospholamban in mice","volume":"291","author":"Larsen","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"118877","DOI":"10.1016\/j.lfs.2020.118877","article-title":"Sacubitril\/valsartan treatment relieved the progression of established pulmonary hypertension in rat model and its mechanism","volume":"266","author":"Liu","year":"2021","journal-title":"Life Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1002\/ame2.12214","article-title":"Animal models of pulmonary hypertension due to left heart disease","volume":"5","author":"Liu","year":"2022","journal-title":"Anim. Model Exp. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1165\/rcmb.2016-0177OC","article-title":"Development of a mouse model of metabolic syndrome, pulmonary hypertension, and heart failure with preserved ejection fraction","volume":"56","author":"Meng","year":"2017","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/hr.2012.30","article-title":"The stroke-prone spontaneously hypertensive rat: still a useful model for post-GWAS genetic studies?","volume":"35","author":"Nabika","year":"2012","journal-title":"Hypertens. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.pupt.2015.09.007","article-title":"Exploring the monocrotaline animal model for the study of pulmonary arterial hypertension: a network approach","volume":"35","author":"Nogueira-Ferreira","year":"2015","journal-title":"Pulm. Pharmacol. Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2859","DOI":"10.1161\/CIRCULATIONAHA.112.109868","article-title":"GRK2-mediated inhibition of adrenergic and dopaminergic signaling in right ventricular hypertrophy: therapeutic implications in pulmonary hypertension","volume":"126","author":"Piao","year":"2012","journal-title":"Circulation"},{"key":"B21","doi-asserted-by":"publisher","first-page":"3667","DOI":"10.1002\/ehf2.14257","article-title":"Heart failure: an update from the last years and a look at the near future","volume":"9","author":"Riccardi","year":"2022","journal-title":"Esc. Heart Fail"},{"key":"B22","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1111\/crj.12406","article-title":"Prevalence of metabolic syndrome in patients with pulmonary hypertension","volume":"11","author":"Satoh","year":"2017","journal-title":"Clin. Respir. J."},{"key":"B23","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1111\/crj.12406","article-title":"Prevalence of metabolic syndrome in patients with pulmonary hypertension","volume":"11","author":"Ussavarungsi","year":"2017","journal-title":"Clin. Respir. J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/S0140-6736(22)01429-5","article-title":"SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials","volume":"400","author":"Vaduganathan","year":"2022","journal-title":"Lancet"},{"key":"B25","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/j.jacbts.2017.07.013","article-title":"Murine models of heart failure with preserved ejection fraction: a \"fishing expedition","volume":"2","author":"Valero-Mu\u00f1oz","year":"2017","journal-title":"JACC Basic. Transl. Sci."},{"key":"B26","doi-asserted-by":"publisher","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":"van Suylen","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1308095\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T05:16:30Z","timestamp":1704690990000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1308095\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,8]]},"references-count":26,"alternative-id":["10.3389\/fphar.2023.1308095"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1308095","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,8]]},"article-number":"1308095"}}