Pulmonary vascular changes in piglets with increased pulmonary blood flow and pressure.
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.
Gorenflo
Matthias
M
Department of Pediatric Cardiology, University Medical Centre, University of Heidelberg, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany. Matthias.Gorenflo@med.uni-heidelberg.de
Herpel
Esther
E
Ullmann
Michael V
MV
Röhlig
Karoline
K
Demirakca
Sueha
S
Klimpel
Homa
H
Hagl
Siegfried
S
Gebhard
Martha Maria
MM
Schnabel
Philipp A
PA
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
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