Fibrinolytic balance of the arterial wall: pulmonary artery displays increased fibrinolytic potential compared with aorta.
Classic pulmonary thromboembolism research has documented that large pulmonary thromboemboli lyse spontaneously, suggesting potent fibrinolytic activity in human pulmonary artery (Pa). This concept conflicts with published animal studies in which the proximal Pa was reported to be devoid of tissue plasminogen activator (t-PA) expression. The current study used in situ hybridization protocols to demonstrate t-PA expression in samples of human main Pa (n = 30). Real-time PCR was used to demonstrate quantitatively that the levels of t-PA transcripts were higher than those of its primary regulator [ie, plasminogen activator-inhibitor 1 (PAI-1)] in the Pa samples. Immunologic and functional assays extended these observations by demonstrating that levels of t-PA antigen were higher than PAI-1 antigen, which resulted in the detection of free t-PA activity. This contrasted with the fibrinolytic balance of matched samples of aorta (n = 6) in which PAI-1 transcripts and antigen values were higher than the corresponding t-PA values, and only M(r) 110 kDa t-PA-PAI-1 complexes could be detected in functional assays. To assess the relative fibrinolytic contribution of the endothelial cell layer, Pa endothelial cells and aortic endothelial cells were scraped and propagated in culture for 20 +/- 6 days. Pa endothelial cell-conditioned media revealed increased t-PA/PAI-1 antigen ratios. Taken together, our data indicate that the balance between t-PA and PAI-1 is shifted in human main Pa to favor net PA activity.
Rosenhek
Raphael
R
Department of Cardiology, University of Vienna, and the Ludwig Boltzmann Institute for Cardiovascular Research, Vienna, Austria.
Korschineck
Irina
I
Gharehbaghi-Schnell
Elisabeth
E
Jakowitsch
Johannes
J
Bonderman
Diana
D
Huber
Kurt
K
Czerny
Martin
M
Schleef
Raymond R
RR
Maurer
Gerald
G
Lang
Irene M
IM
D001013:Aorta, Thoracic / Q000502:physiology*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000502:physiology*; D005342:Fibrinolysis / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D017403:In Situ Hybridization; D009928:Organ Specificity; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000235:genetics; D016133:Polymerase Chain Reaction; D011651:Pulmonary Artery / Q000502:physiology*; D014019:Tissue Donors; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000235:genetics; D014158:Transcription, Genetic
D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator