Vascular endothelial growth factor-B-deficient mice show impaired development of hypoxic pulmonary hypertension

doi:10.1016/S0008-6363(02)00440-6

Cardiovascular Research 2002 55(2):361-368; doi:10.1016/S0008-6363(02)00440-6
© 2002 by European Society of Cardiology

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Vascular endothelial growth factor-B-deficient mice show impaired development of hypoxic pulmonary hypertension

Janet C Wanstall^a^,*, Agatha Gambino^a, Trina K Jeffery^a^,1, Marian M Cahill^b, Daniela Bellomo^b^,2, Nicholas K Hayward^b and Graham F Kay^b

^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 tothe pulmonary vascular remodelling, and the associated pulmonaryhypertension, induced by exposure of mice to chronic hypoxia.Methods: Right ventricular systolic pressure, the ratio of rightventricle/[left ventricle+septum] (RV/[LV+S]) and the thicknessof the media (relative to vessel diameter) of intralobar pulmonaryarteries (o.d. 50–150 and 151–420 µm) weredetermined in Vegfb knockout mice (Vegfb^–/–; n =17) and corresponding wild-type mice (Vegfb^+/+; n = 17) exposedto chronic hypoxia (10% oxygen) or housed in room air (normoxia)for 4 weeks. Results: In Vegfb^+/+ mice hypoxia caused (i) pulmonaryhypertension (a 70% increase in right ventricular systolic pressurecompared with normoxic Vegfb^+/+ mice; P<0.001), (ii) rightventricular hypertrophy (a 66% increase in RV/[LV+S]; P<0.001)and (iii) pulmonary vascular remodelling (a 27–36% increasein pulmonary arterial medial thickness; P<0.05). In contrast,in Vegfb^–/– mice hypoxia did not cause any increasein either right ventricular systolic pressure or pulmonary arterialmedial thickness; also right ventricular hypertrophy (41% increasein RV/[LV+S]; P<0.001) was less pronounced (P<0.05) thanin Vegfb^+/+ mice. Conclusion: Vegf-B may have a role in thedevelopment of chronic hypoxic pulmonary hypertension in miceby contributing to pulmonary vascular remodelling. If so, theeffect of Vegf-B appears to be different from that of Vegf-Awhich is reported to protect against, rather than contributeto, 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, 20132Milan, Italy.

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