| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pediatrics, Northwestern University, Chicago, IL, USA
2 Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA
3 Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA; Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA
4 Department of Pediatrics, Northwestern University, Chicago, IL, USA; Department of Molecular Pharmacology, Northwestern University, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: steveblack{at}northwestern.edu.
Utilizing in utero aortopulmonary vascular graft placement, we have developed a lamb model of congenital heart disease and increased pulmonary blood flow (shunt lambs). We have previously shown that these lambs have alterations in pulmonary vessel number at 4-weeks of age compared to age matched control lambs. To determine if alterations in vascular endothelial growth (VEGF) was associated with this vascular remodeling we have investigated vascular changes in expression and VEGF and its receptors, Flt-1 and KDR/Flk-1 in the lungs of shunted and age matched control lambs during the first 8-weeks of life. Western blot analysis demonstrated that VEGF, Flt-1 and KDR/Flk-1 expression were higher in the shunt as compared to control lambs. VEGF and Flt-1 expression were increased at 4-and 8-weeks of age (P<0.05). However, KDR/Flk-1 expression in the shunt lambs was higher than control values at 1- and 4-weeks, and decreased at 8-weeks of age (P<0.05). Immunohistochemical analysis demonstrated that VEGF localized mainly to the smooth muscle layer of vessels and airways as well as in pulmonary epithelium, in both controls and shunts. Compared to controls, shunt lambs have increased VEGF in the smooth muscle layer of thickened media of small pulmonary arteries (remodeled vessels), but not of large veins or arteries, nor in the airways. VEGF receptors were localized exclusively in the endothelium of capillaries and pulmonary vessels. Compared to controls, Flt-1 was increased in the endothelium of small pulmonary arteries in shunt animals at 4- and 8-weeks of age, while KDR/Flk-1 was found to be increased predominantly in small pulmonary arteries at 1- and 4-weeks of age. Our data suggest that increased pulmonary blood flow up-regulates the expression of VEGF and its receptors and this event may be important in the development of the abnormal pulmonary vasculature associated with the progression of pulmonary hypertension.
This article has been cited by other articles:
|
|
 |
|
  L. Ray, M. Mathieu, P. Jespers, I. Hadad, M. Mahmoudabady, A. Pensis, S. Motte, I. R. Peters, R. Naeije, and K. McEntee Early increase in pulmonary vascular reactivity with overexpression of endothelin-1 and vascular endothelial growth factor in canine experimental heart failure Exp Physiol, March 1, 2008; 93(3): 434 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Black, J. M. DeVol, and S. Wedgwood Regulation of fibroblast growth factor-2 expression in pulmonary arterial smooth muscle cells involves increased reactive oxygen species generation Am J Physiol Cell Physiol, January 1, 2008; 294(1): C345 - C354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T.R. Roofthooft, K. A. Bergman, T. W. Waterbolk, T. Ebels, B. Bartelds, and R. M.F. Berger Persistent Pulmonary Hypertension of the Newborn With Transposition of the Great Arteries Ann. Thorac. Surg., April 1, 2007; 83(4): 1446 - 1450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Majka, K. Fox, B. McGuire, J. Crossno Jr., P. McGuire, and A. Izzo Pleiotropic role of VEGF-A in regulating fetal pulmonary mesenchymal cell turnover Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1183 - L1192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-F. Lam, T. E. Peterson, A. J. Croatt, K. A. Nath, and Z. S. Katusic Functional adaptation and remodeling of pulmonary artery in flow-induced pulmonary hypertension Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2334 - H2341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Mata-Greenwood, A. Grobe, S. Kumar, Y. Noskina, and S. M. Black Cyclic stretch increases VEGF expression in pulmonary arterial smooth muscle cells via TGF-{beta}1 and reactive oxygen species: a requirement for NAD(P)H oxidase Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L288 - L289. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
