HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/1/L222    most recent 00388.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (18) Citing Articles via Google Scholar Google Scholar Articles by Mata-Greenwood, E. Articles by Black, S. M. Search for Related Content PubMed PubMed Citation Articles by Mata-Greenwood, E. Articles by Black, S. M.

Expression of VEGF and its receptors Flt-1 and Flk-1/KDR is altered in lambs with increased pulmonary blood flow and pulmonary hypertension

Departments of ¹Pediatrics and ⁵Molecular Pharmacology, Northwestern University, Chicago, Illinois 60611-3008; ²Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2650; and ³Department of Pediatrics and ⁴Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143-0106

Submitted 15 November 2002 ; accepted in final form 24 March 2003

Utilizing in utero aortopulmonary vascular graft placement, we developed a lamb model of congenital heart disease and increased pulmonary blood flow. We showed previously that these lambs have increased pulmonary vessel number at 4 wk of age. To determine whether this was associated with alterations in VEGF signaling, we investigated vascular changes in expression of VEGF and its receptors, Flt-1 and KDR/Flk-1, in the lungs of shunted and age-matched control lambs during the first 8 wk of life. Western blot analysis demonstrated that VEGF, Flt-1, and KDR/Flk-1 expression was higher in shunted lambs. VEGF and Flt-1 expression was increased at 4 and 8 wk of age (P <0.05). However, KDR/Flk-1 expression was higher in shunted lambs only at 1 and 4 wk of age (P <0.05). Immunohistochemical analysis demonstrated that, in control and shunted lambs, VEGF localized to the smooth muscle layer of vessels and airways and to the pulmonary epithelium while increased VEGF expression was localized to the smooth muscle layer of thickened media in remodeled vessels in shunted lambs. VEGF receptors were localized exclusively in the endothelium of pulmonary vessels. Flt-1 was increased in the endothelium of small pulmonary arteries in shunted animals at 4 and 8 wk of age, whereas KDR/Flk-1 was increased in small pulmonary arteries at 1 and 4 wk of age. Our data suggest that increased pulmonary blood flow upregulates expression of VEGF and its receptors, and this may be important in development of the vascular remodeling in shunted lambs.

vascular graft placement; shunted lambs

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]