Hemodynamics and the Role of Vascular Injury in Pulmonary Artery Remodeling in Rats

Abstract

Diffuse neointimal lesions including smooth muscle cells expressing extracellular matrix genes describe vascular remodeling in adult human
elastic pulmonary arteries. It has recently come to light that vascular damage is necessary to kick off the remodeling process, and that growth
factor mediators play a role in the healing process. However, it has been postulated that systemic-like hemodynamic circumstances are also
required since neointimal development is only found in individuals with pulmonary artery blood pressures reaching systemic values. To
examine this, Sprague-Dawley rats were subjected to three experimental situations in which subclavian-pul- monary artery anastomoses were
performed: with no concomitant damage, after injury with monocrotaline, and after injury with balloon end-arterectomy.
The anastomosis between the subclavian and pulmonary arteries did not alone cause pulmonary vascular remodeling. In the presence of the
anastomosis, the remodeling pattern after moderate monocrotaline-induced damage shifted from being non-neointimal to being neointimal.
After severe, balloon endarterectomy-induced damage, neointima was also seen even in the absence of anastomosis. Expression of
tropoelastin, type I procollagen, and transforming growth factor beta, as well as immunoreactivity for angiotensin converting enzyme, was
localized to the neointima, much as it is in human hypertension elastic pulmonary arteries. arterial neointimal lesions. These findings bring
the idea that the elastic response of the pulmonary artery to injury may be affected by both the nature of the lesion and the underlying
hemody- namic circumstances. (J. Clinical Invest. 1996;98:436-442) Pulmonary hypertension, neointima, extracellular matrix,
monocrotaline, vascular damage.