VEGF in the lung: a role for novel isoforms.
Vascular endothelial cell growth factor (VEGF) is a potent mitogen and permogen that increases in the plasma and decreases in the alveolar space in respiratory diseases such as acute respiratory distress syndrome (ARDS). This observation has led to controversy over the role of this potent molecule in lung physiology and disease. We hypothesized that some of the VEGF previously detected in normal lung may be of the anti-angiogenic family (VEGF(xxx)b) with significant potential effects on VEGF bioactivity. VEGF(xxx)b protein expression was assessed by indirect immunohistochemistry in normal and ARDS tissue. Expression of VEGF(xxx)b was also detected by immunoblotting in normal lung tissue, primary human alveolar type II (ATII) cells, and bronchoalveolar lavage (BAL) fluid in normal subjects and by ELISA in normal, "at risk," and ARDS subjects. The effect of VEGF(165) and VEGF(165)b on both human primary endothelial cells and alveolar epithelial cell proliferation was assessed by [(3)H]thymidine uptake. We found that VEGF(165)b was widely expressed in normal healthy lung tissue but is reduced in ARDS lung. VEGF(121)b and VEGF(165)b were present in whole lung, BAL, and ATII lysate. The proliferative effect of VEGF(165) on both human primary endothelial cells and human alveolar epithelial cells was significantly inhibited by VEGF(165)b (P < 0.01). These data demonstrate that the novel VEGF(xxx)b family members are expressed in normal lung and are reduced in ARDS. A specific functional effect on primary human endothelial and alveolar epithelial cells has also been shown. These data suggest that the VEGF(xxx)b family may have a role in repair after lung injury.
Lung Research Group, Department of Clinical Science at North Bristol, University of Bristol Paul O'Gorman Lifeline Centre, Southmead Hospital, Westbury-on-Trym, United Kingdom.
Julia
J
Varet
Samantha K
SK
Douglas
Laura
L
Gilmartin
Andrew R L
AR
Medford
David O
DO
Bates
Steven J
SJ
Harper
Ann B
AB
Millar
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism*; D055370:Lung Injury / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D042442:Vascular Endothelial Growth Factors / Q000096:biosynthesis* / Q000378:metabolism
D020033:Protein Isoforms; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors