Abstract
Pulmonary hypertension (PH) is a devastating disease, characterized by complex remodeling of the pulmonary vasculature. PH is classified into five groups based on different etiology, pathology, as well as therapy and prognosis. Animal models are essential for the study of underlying mechanisms, pathophysiology, and preclinical testing of new therapies for PH. The complexity of the disease with different clinical entities dictates the necessity for more than one animal model to resemble PH, as a single model cannot imitate the broad spectrum of human PH.
Here we describe a detailed protocol for creating a rat model of PH with right ventricular (RV) failure. Furthermore, we present how to characterize it hemodynamically by invasive measurements of RV and pulmonary arterial (PA) pressures. Animals subjected to this model display severe pulmonary vascular remodeling and RV dysfunction. In this model, rats undergo a single subcutaneous injection of Sugen (SU5416, a vascular endothelial growth factor inhibitor) and are immediately exposed to chronic hypoxia in a hypoxia chamber for 3–6 weeks. This Sugen/Hypoxia rat model resembles Group 1 PH.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Humbert M et al (2022) 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 43(38):3618–3731. https://doi.org/10.1093/eurheartj/ehac237
Simonneau G et al (2019) Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J 53(1). https://doi.org/10.1183/13993003.01913-2018
Wijeratne DT et al (2018) Increasing incidence and prevalence of World Health Organization Groups 1 to 4 pulmonary hypertension: a population-based cohort study in Ontario, Canada. Circ Cardiovasc Qual Outcomes 11(2):e003973. https://doi.org/10.1161/CIRCOUTCOMES.117.003973
Stenmark KR et al (2009) Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure. Am J Phys Lung Cell Mol Phys 297(6):L1013–L1032. https://doi.org/10.1152/ajplung.00217.2009
Boucherat O, Agrawal V, Lawrie A, Bonnet S (2022) The latest in animal models of pulmonary hypertension and right ventricular failure. Circ Res 130(9):1466–1486. https://doi.org/10.1161/CIRCRESAHA.121.319971
Ryan J, Bloch K, Archer SL (2011) Rodent models of pulmonary hypertension: harmonisation with the World Health Organisation’s categorisation of human PH. Int J Clin Pract Suppl 172:15–34. https://doi.org/10.1111/j.1742-1241.2011.02710.x
Colvin KL, Yeager ME (2014) Animal models of pulmonary hypertension: matching disease mechanisms to etiology of the human disease. J Pulm Respir Med 4(4). https://doi.org/10.4172/2161-105X.1000198
Suen CM et al (2019) Fischer rats exhibit maladaptive structural and molecular right ventricular remodelling in severe pulmonary hypertension: a genetically prone model for right heart failure. Cardiovasc Res 115(4):788–799. https://doi.org/10.1093/cvr/cvy258
Jiang B et al (2016) Marked strain-specific differences in the SU5416 rat model of severe pulmonary arterial hypertension. Am J Respir Cell Mol Biol 54(4):461–468. https://doi.org/10.1165/rcmb.2014-0488OC
Taraseviciene-Stewart L et al (2001) Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death-dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension. FASEB J 15(2):427–438. https://doi.org/10.1096/fj.00-0343com
Kojonazarov B et al (2019) Severe emphysema in the SU5416/hypoxia rat model of pulmonary hypertension. Am J Respir Crit Care Med 200(4):515–518. https://doi.org/10.1164/rccm.201902-0390LE
Kasahara Y et al (2000) Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest 106(11):1311–1319. https://doi.org/10.1172/JCI10259
Kilkenny C et al (2010) Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 8(6):e1000412. https://doi.org/10.1371/journal.pbio.1000412
Acknowledgments
This work was supported by a DZHK Grant to O.B. and grants NIH-K01HL135474, AHA-20TPA35520000 and NIH-R01HL160963 to Y.S.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2024 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Bikou, O., Sassi, Y. (2024). The Sugen/Hypoxia Rat Model for Pulmonary Hypertension and Right Heart Failure. In: Ishikawa, K. (eds) Experimental Models of Cardiovascular Diseases. Methods in Molecular Biology, vol 2803. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3846-0_12
Download citation
DOI: https://doi.org/10.1007/978-1-0716-3846-0_12
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-3845-3
Online ISBN: 978-1-0716-3846-0
eBook Packages: Springer Protocols