title: Pulmonary vascular changes in piglets with increased pulmonary blood flow and pressure.
abstract: In this model of pulmonary vascular disease, high pulmonary blood flow was created by an anastomosis between the left subclavian artery and the main pulmonary artery [Blalock-Taussig (BT) shunt] in 4-week-old piglets (n = 6). Additional ligation of the left pulmonary artery (LPA) was used to increase pulmonary artery pressure (n = 6). Seven piglets were sham-operated. After 3 months, mean pulmonary artery pressure was higher in animals with BT shunt and LPA ligation (22 +/- 5; mean+/-SD) compared to sham-operated animals (15 +/- 2). In addition, thickening of the medial coat (20.1 +/- 2.8% versus 13.6 +/- 3.1% wall thickness) and increased immunostaining for vascular endothelial growth factor A (VEGF-A) were observed. Relative gene expression for endothelin-converting enzyme-1 (ECE-1) mRNA was 1.8 times higher, and VEGF-A mRNA was 2.5 times higher in pigs with BT shunt and LPA ligation compared with sham-operated animals. VEGF receptor-1 and VEGF receptor-2 mRNA was lower in shunted animals and in animals with additional ligation of LPA. Upregulation of ECE-1 and VEGF-A, as well as changes in VEGFR expression in the pulmonary hypertensive lung, may contribute to pulmonary vascular changes.
authors: Department of Pediatric Cardiology, University Medical Centre, University of Heidelberg, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany. Matthias.Gorenflo@med.uni-heidelberg.de
authors: Matthias
authors: M
authors: Gorenflo
authors: Esther
authors: E
authors: Herpel
authors: Michael V
authors: MV
authors: Ullmann
authors: Karoline
authors: K
authors: Röhlig
authors: Sueha
authors: S
authors: Demirakca
authors: Homa
authors: H
authors: Klimpel
authors: Siegfried
authors: S
authors: Hagl
authors: Martha Maria
authors: MM
authors: Gebhard
authors: Philipp A
authors: PA
authors: Schnabel
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D001794:Blood Pressure; D006152:Cyclic GMP / Q000097:blood; D019332:Endothelin-1 / Q000097:blood; D000072396:Endothelin-Converting Enzymes; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D007527:Isoenzymes / Q000235:genetics; D008168:Lung / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology*; D011652:Pulmonary Circulation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
chemical_list: D019332:Endothelin-1; D007527:Isoenzymes; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; D006152:Cyclic GMP