Xiao-Qing Sun, Timothy Klouda, Suzanne Barnasconi, Ingrid Schalij, Janne Schwab, Anders Hammer Nielsen-Kudsk, Julie Sørensen Axelsen, Asger Andersen, Jurjan Aman, Frances S. de Man, Harm Jan Bogaard, Ke Yuan, Keimei Yoshida
Amsterdam UMC. Boston Children’s Hospital. Aarhus University Hospital.
Netherlands, United States and Denmark
American Journal of Physiology Lung Cellular and Molecular Physiology
Am J Physiol Lung Cell Mol Physiol 2024;
DOI: 10.1152/ajplung.00105.2024
Abstract
In the field of pulmonary hypertension (PH), a well-established protocol to induce severe angioproliferation in rats (SuHx) involves combining the VEGF-R inhibitor Sugen 5416 (SU5416) with three weeks of hypoxia (Hx). Additionally, injecting monocrotaline (MCT) into rats can induce inflammation and shear stress in the pulmonary vasculature, leading to neointima-like remodeling. However, the SuHx protocol in mice is still controversial, with some studies suggesting it yields higher and reversible PH than Hx alone, possibly due to species-dependent hypoxic responses. To establish an alternative rodent model of PH, we hypothesized mice would be more sensitive to hemodynamic changes secondary to shear stress compared to Hx. We attempted to induce severe and irreversible PH in mice by combining SU5416 or monocrotaline pyrrole (MCTP) injection with pneumonectomy (PNx). However, our experiments showed SU5416 administered to mice at various time points after PNx did not result in severe PH. Similarly, mice injected with MCTP after PNx (MPNx) showed no difference in right ventricular systolic pressure or exacerbated pulmonary vascular remodeling compared to PNx alone. These findings collectively demonstrate that C57/B6 mice do not develop severe and persistent PH when PNx is combined with either SU5416 or MCTP.
Category
Animal Models of Pulmonary Vascular Disease and Therapy
Class I. Drug-induced and Toxin-induced Pulmonary Hypertension
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
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