Research article summary (published 20 Jun 2007):

Plexiform-like lesions and increased tissue factor expression in a rat model of severe pulmonary arterial hypertension.

Full Abstract

Severe pulmonary arterial hypertension (PAH) occurs in idiopathic form and in association with diverse diseases. The pathological hallmarks are distal smooth muscle hypertrophy, obliteration of small pulmonary arteriole lumens, and disorganized cellular proliferation in plexiform lesions. In situ thrombosis is also observed. A detailed understanding of the disease progression has been hampered by the absence of an animal model bearing all the pathological features of human disease. To create a model with these characteristics, we gave young (200-g) rats monocrotaline 1 wk following left pneumonectomy; controls with vehicle treatment or sham operation were also studied. In experimental rats, pulmonary arteries had distal smooth muscle hypertrophy and proliferative perivascular lesions. The lesions had a plexiform appearance, occurred early in disease development, and were composed of cells expressing endothelial antigens. Three-dimensional microangiography revealed severe vascular pruning and disorganized vascular networks. We found that expression of tissue factor (TF), the membrane glycoprotein that initiates coagulation, facilitates angiogenesis, and mediates arterial injury in the systemic circulation, was increased in the pulmonary arterioles and plexiform-like lesions of the rats. TF was also heavily expressed in the vessels and plexiform lesions of humans with pulmonary arterial hypertension. We conclude that plexiform-like lesions can be reproduced in rats, and this model will facilitate experiments to address controversies about the role of these lesions in PAH. Increased TF expression may contribute to the prothrombotic diathesis and vascular cell proliferation typical of human disease.

Author information

Author/s: White, R James (RJ); Meoli, David F (DF); Swarthout, Robert F (RF); Kallop, Dara Y (DY); Galaria, Irfan I (II); Harvey, Jennifer L (JL); Miller, Christine M (CM); Blaxall, Burns C (BC); Hall, Carla M (CM); Pierce, Richard A (RA); Cool, Carlyne D (CD); Taubman, Mark B (MB);

Affiliation: Division of Pulmonary and Critical Care Medicine, Univ. of Rochester, 601 Elmwood Ave., Box 692, Rochester, NY, USA. Jim_White(-atsign-)urmc.rochester.edu

Grants: P50-HL-54469-06 (Agency:NHLBI NIH HHS) ; T32-HL-66988 (Agency:NHLBI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol), published in United States. (Language: eng)

Reference: 2007-Sep; vol 293 (issue 3) : pp L583-90

Dates: Created 2007/08/30; Completed 2007/10/17; Revised 2007/12/03;

PMID: 17586694, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

CommentIn: Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L580-2. (PMID: 17660327)

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Angiography Animals Cell Proliferation - drug effects Disease Models, Animal Endothelial Cells - metabolism; pathology Humans Hypertension, Pulmonary - chemically induced; metabolism; pathology Hypertrophy, Right Ventricular - chemically induced; pathology Male

Male Monocrotaline - administration & dosage; pharmacology Pneumonectomy Pulmonary Artery - drug effects; metabolism; pathology; radiography Rats Rats, Sprague-Dawley Thromboplastin - metabolism Vascular Endothelial Growth Factor Receptor-2 - metabolism von Willebrand Factor - metabolism

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: von Willebrand Factor (0) ; Monocrotaline (315-22-0) ; Thromboplastin (9035-58-9) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.1.112)

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