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

J Clin Invest. 1996 Jul 15;98(2):434-42. doi: 10.1172/JCI118809.


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-beta 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anastomosis, Surgical
  • Animals
  • Blood Pressure / drug effects
  • Endarterectomy / adverse effects
  • Gene Expression
  • Hemodynamics*
  • Humans
  • In Situ Hybridization
  • Lung / blood supply*
  • Male
  • Microscopy, Electron
  • Monocrotaline / pharmacology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / injuries
  • Muscle, Smooth, Vascular / physiology*
  • Procollagen / biosynthesis
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / injuries*
  • Pulmonary Artery / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow
  • Subclavian Artery / drug effects
  • Subclavian Artery / physiology
  • Transforming Growth Factor beta / biosynthesis
  • Tropoelastin / analysis


  • Procollagen
  • Transforming Growth Factor beta
  • Tropoelastin
  • Monocrotaline