Enhanced expression of vascular endothelial growth factor in pulmonary plexogenic arteriopathy due to congenital heart disease

Congenital heart disease (CHD) leading to increased pulmonary blood pressur e and flow is an important cause of pulmonary plexogenic arteriopathy (PPA) , This type of arteriopathy tends to progress to an irreversible stage, hal lmarked histologically by the emergence of a number of characteristic lesio ns, which include concentric laminar intimal proliferation and fibrosis, an d plexiform lesions. The pathogenesis of these lesions, which connote a ver y poor prognosis, is not well understood. Since endothelial cell proliferat ion has been demonstrated in these lesions, it was hypothesized that vascul ar endothelial growth factor (VEGF), a key mediator of angiogenesis, might play a role in their pathogenesis, Thirty-nine patients with various types of CHD, who underwent cardiac catheterization and subsequent cardiac surger y, were studied prospectively. On the basis of a detailed assessment of the type of cardiac defect, the haemodynamic abnormalities, and the histopatho logical features evident from open lung biopsies, taken in all instances, p atients were histologically grouped into cases with moderate PPA (n=18), ad vanced PPA (n=7), pulmonary congestive vasculopathy (PCV, n=5), and control s lacking pulmonary hypertension or increased pulmonary blood flow (n=4), F ive patients were excluded from analysis because of inadequate sample size or quality. The presence of VECF was assessed immunohistochemically using s tandard procedures and was correlated with haemodynamic and histological da ta. Immunoreactive VEGF was detected in pulmonary arterial smooth muscle ce lls and endothelial cells in 13 out of 34 cases and was more frequent and m ore pronounced in patients with the histological lesions of advanced PPA th an in those with moderate PPA (p<0.01). VEGF positivity was particularly pr ominent in the lesions characteristic of advanced PPA, No difference in VEG F expression was observed between controls, PVC, and moderate PPA cases. Me asured haemodynamic parameters did not differ significantly between VEGF-po sitive and VEGF-negative cases. We conclude that VEGF may play a role in th e angioproliferative changes of advanced PPA, Copyright (C) 2000 John Wiley & Sons, Ltd.