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


CONCLUSIONS
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.
Wanstall
Janet C
JC
School of Biomedical Sciences, Department of Physiology and Pharmacology, University of Queensland, St. Lucia, Qld. 4072, Brisbane, Australia. wanstall@mailbox.uq.edu.au
Gambino
Agatha
A
Jeffery
Trina K
TK
Cahill
Marian M
MM
Bellomo
Daniela
D
Hayward
Nicholas K
NK
Kay
Graham F
GF
D000818:Animals; D002908:Chronic Disease; D016228:Endothelial Growth Factors / Q000502:physiology*; D005260:Female; D006400:Hematocrit; D006976:Hypertension, Pulmonary / Q000473:pathology / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology; D011652:Pulmonary Circulation; D017540:Tunica Media / Q000473:pathology; D042561:Vascular Endothelial Growth Factor B
D016228:Endothelial Growth Factors; D042561:Vascular Endothelial Growth Factor B