Pulmonary veins in the normal lung and pulmonary hypertension due to left heart disease

James M. Hunt, Brian Bethea, Xiang Liu, Aneta Gandjeva, Pradeep P A Mammen, Elvira Stacher, Marina R. Gandjeva, Elisabeth Parish, Mario Perez, Lynelle Smith, Brian B. Graham, Wolfgang M. Kuebler, Rubin M. Tuder

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)L725-L736
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume305
Issue number10
DOIs
StatePublished - Nov 15 2013

Keywords

  • Left heart failure
  • Pulmonary circulation
  • Pulmonary hypertension
  • Pulmonary veins
  • Vessel remodeling

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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  • Cite this

    Hunt, J. M., Bethea, B., Liu, X., Gandjeva, A., Mammen, P. P. A., Stacher, E., Gandjeva, M. R., Parish, E., Perez, M., Smith, L., Graham, B. B., Kuebler, W. M., & Tuder, R. M. (2013). Pulmonary veins in the normal lung and pulmonary hypertension due to left heart disease. American Journal of Physiology - Lung Cellular and Molecular Physiology, 305(10), L725-L736. https://doi.org/10.1152/ajplung.00186.2013