© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Vascular endothelial growth factor-B-deficient mice show impaired development of hypoxic pulmonary hypertension
aSchool of Biomedical Sciences, Department of Physiology and Pharmacology, University of Queensland, St. Lucia, Brisbane, Qld. 4072, Australia
bQCF Transgenic Laboratory, Joint Experimental Oncology Program, The Queensland Institute of Medical Research and the University of Queensland, Brisbane, Australia
wanstall{at}mailbox.uq.edu.au
* Corresponding author. Tel.: +61-7-3365-3113; fax: +61-7-3365-1766
Objective: To test the hypothesis that Vegf-B contributes to the pulmonary vascular remodelling, and the associated pulmonary hypertension, induced by exposure of mice to chronic hypoxia. Methods: Right ventricular systolic pressure, the ratio of right ventricle/[left ventricle+septum] (RV/[LV+S]) and the thickness of the media (relative to vessel diameter) of intralobar pulmonary arteries (o.d. 50–150 and 151–420 µm) were determined in Vegfb knockout mice (Vegfb–/–; n = 17) and corresponding wild-type mice (Vegfb+/+; n = 17) exposed to chronic hypoxia (10% oxygen) or housed in room air (normoxia) for 4 weeks. Results: In Vegfb+/+ mice hypoxia caused (i) pulmonary hypertension (a 70% increase in right ventricular systolic pressure compared with normoxic Vegfb+/+ mice; P<0.001), (ii) right ventricular hypertrophy (a 66% increase in RV/[LV+S]; P<0.001) and (iii) pulmonary vascular remodelling (a 27–36% increase in pulmonary arterial medial thickness; P<0.05). In contrast, in Vegfb–/– mice hypoxia did not cause any increase in either right ventricular systolic pressure or pulmonary arterial medial thickness; also right ventricular hypertrophy (41% increase in RV/[LV+S]; P<0.001) was less pronounced (P<0.05) than in Vegfb+/+ mice. Conclusion: Vegf-B may have a role in the development of chronic hypoxic pulmonary hypertension in mice by contributing to pulmonary vascular remodelling. If so, the effect of Vegf-B appears to be different from that of Vegf-A which is reported to protect against, rather than contribute to, hypoxia-induced pulmonary vascular remodelling.
KEYWORDS Growth factors; Hypertrophy; Hypoxia; Pulmonary circulation; Remodelling
1 Current address: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
2 Current address: Science Park Raf Spa, Via Olgettina 558, 20132 Milan, Italy.
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