title: Pulmonary veins in the normal lung and pulmonary hypertension due to left heart disease.
abstract: Despite the importance of pulmonary veins in normal lung physiology and the pathobiology of pulmonary hypertension with left heart disease (PH-LHD), pulmonary veins remain largely understudied. Difficult to identify histologically, lung venous endothelium or smooth muscle cells display no unique characteristic functional and structural markers that distinguish them from pulmonary arteries. To address these challenges, we undertook a search for unique molecular markers in pulmonary veins. In addition, we addressed the expression pattern of a candidate molecular marker and analyzed the structural pattern of vascular remodeling of pulmonary veins in a rodent model of PH-LHD and in lung tissue of patients with PH-LHD obtained at time of placement on a left ventricular assist device. We detected urokinase plasminogen activator receptor (uPAR) expression preferentially in normal pulmonary veins of mice, rats, and human lungs. Expression of uPAR remained elevated in pulmonary veins of rats with PH-LHD; however, we also detected induction of uPAR expression in remodeled pulmonary arteries. These findings were validated in lungs of patients with PH-LHD. In selected patients with sequential lung biopsy at the time of removal of the left ventricular assist device, we present early data suggesting improvement in pulmonary hemodynamics and venous remodeling, indicating potential regression of venous remodeling in response to assist device treatment. Our data indicate that remodeling of pulmonary veins is an integral part of PH-LHD and that pulmonary veins share some key features present in remodeled yet not normotensive pulmonary arteries.
authors.affiliation: Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, Univ. of Colorado Denver, Anschutz Medical Campus, Research 2 - 9th floor, Rm. 9001; Mail stop C-272, 12700 East 19th Ave., Aurora, CO 80045. rubin.tuder@ucdenver.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Hunt
authors.forename: Brian
authors.initials: B
authors.lastname: Bethea
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.forename: Aneta
authors.initials: A
authors.lastname: Gandjeva
authors.forename: Pradeep P A
authors.initials: PP
authors.lastname: Mammen
authors.forename: Elvira
authors.initials: E
authors.lastname: Stacher
authors.forename: Marina R
authors.initials: MR
authors.lastname: Gandjeva
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Parish
authors.forename: Mario
authors.initials: M
authors.lastname: Perez
authors.forename: Lynelle
authors.initials: L
authors.lastname: Smith
authors.forename: Brian B
authors.initials: BB
authors.lastname: Graham
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Kuebler
authors.forename: Rubin M
authors.initials: RM
authors.lastname: Tuder
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation; D002648:Child; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006331:Heart Diseases / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D006353:Heart-Assist Devices; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000473:pathology* / Q000628:therapy; D007124:Immunoenzyme Techniques; D061346:Laser Capture Microdissection; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology*; D011667:Pulmonary Veins / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D055293:Receptors, Urokinase Plasminogen Activator
keywords: left heart failure; pulmonary circulation; pulmonary hypertension; pulmonary veins; vessel remodeling
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