Role of VEGF-B in the lung during development of chronic hypoxic pulmonary hypertension.
Angiogenic factors exert protective effects on the lung. To investigate the effect of VEGF-B, a factor coexpressed in the lung with VEGF-A, we assessed chronic hypoxic pulmonary hypertension in VEGF-B knockout mice (VEGF-B-/-) and in rats with lung overexpression of VEGF-B induced by adenovirus transfer. No significant difference in pulmonary hemodynamics, right ventricular hypertrophy, distal vessel muscularization, or vascular density was found between VEGF-B-/- and control mice after 3 wk of hypoxia. When overexpressed, VEGF-B(167) or VEGF-B(186) had protective effects similar to those of human VEGF-A(165). Lung endothelial nitric oxide synthase (eNOS) expression was increased by 5 days of hypoxia or VEGF-A adenovirus vector (Ad.VEGF-A) overexpression, whereas VEGF-B(167) or VEGF-B(186) had no effect. With hypoxia or normoxia, the wet-to-dry lung weight ratio was increased 5 days after Ad.VEGF-A administration compared with control (Ad.nul), Ad.VEGF-B(167), or Ad.VEGF-B(186). Endogenous VEGF-B does not counteract the development of hypoxic pulmonary hypertension. However, when overexpressed in the lung, VEGF-B can be as potent as VEGF-A in attenuating pulmonary hypertension, although it has no effect on eNOS expression or vascular permeability.
Louzier
Vanessa
V
Département de Physiologie, Institut National de la Santé et de La Recherche Médicale Unité 492, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, 94010 Créteil, France.
Raffestin
Bernadette
B
Leroux
Aude
A
Branellec
Didier
D
Caillaud
Jean Michel
JM
Levame
Micheline
M
Eddahibi
Saadia
S
Adnot
Serge
S
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002199:Capillary Permeability / Q000502:physiology; D002908:Chronic Disease; D003587:Cytomegalovirus / Q000235:genetics; D016228:Endothelial Growth Factors / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011401:Promoter Regions, Genetic / Q000235:genetics; D011651:Pulmonary Artery / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000502:physiology; D011654:Pulmonary Edema / Q000378:metabolism / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B
D016228:Endothelial Growth Factors; C467485:VEGFB protein, human; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse