The role of vascular injury and hemodynamics in rat pulmonary artery remodeling

Yoshihiro Tanaka, Daniel P. Schuster, Elaine C. Davis, G. Alexander Patterson, Mitchell D. Botney

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Vascular remodeling in adult human elastic pulmonary arteries is characterized by diffuse neointimal lesions containing smooth muscle cells expressing extracellular matrix genes. Recent studies suggest vascular injury is needed to initiate remodeling and that growth factor mediators participate in the repair response. However, because neointimal formation is only observed in patients with pulmonary artery blood pressures approaching systemic levels, it has been hypothesized that systemic-like hemodynamic conditions are also necessary. To test that hypothesis, subclavian-pulmonary artery anastomoses were created in Sprague-Dawley rats under three different experimental conditions: no accompanying injury, or after monocrotaline or balloon endarterectomy injury. Pulmonary vascular remodeling was not induced by the subclavian-pulmonary artery anastomosis alone. A non-neointimal pattern of remodeling after mild monocrotaline-induced injury was converted into a neointimal pattern in the presence of the anastomosis. Neointima was also observed after severe, balloon endarterectomy-induced injury even in the absence of anastomosis. Tropoelastin, type I procollagen and TGF-β gene expression, and angiotensin converting enzyme immunoreactivity, was confined to the neointima resembling the pattern of gene expression and immunoreactivity in human hypertensive elastic pulmonary artery neointimal lesions. These observations introduce the concepts that the type of injury and the associated hemodynamic conditions can modify the elastic pulmonary artery response to injury.

Original languageEnglish
Pages (from-to)434-442
Number of pages9
JournalJournal of Clinical Investigation
Volume98
Issue number2
DOIs
StatePublished - Jul 15 1996

Keywords

  • extracellular matrix
  • monocrotaline
  • neointima
  • pulmonary hypertension
  • vascular injury

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