Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: evidence for a process of disordered angiogenesis

Pulmonary arteries of patients with severe pulmonary hypertension (SPH) pre senting in an idiopathic form (primary PH-PPH) or associated with congenita l heart malformations or collagen vascular diseases show plexiform lesions. It its postulated that in lungs with SPH, endothelial cells in plexiform l esions express genes encoding; for proteins involved in angiogenesis, in pa rticular, vascular endothelial growth factor (VEGF) and those involved in V EGF receptor-2 (VEGFR-2) signalling. On immunohistochemistry and in. situ h ybridization, endothelial cells in the plexiform lesions expressed VEGF mRN A and protein and overexpressed the mRNA and protein of VEGFR-2, and the tr anscription factor subunits HIF-1 alpha and HIF-1 beta of hypoxia inducible factor, which are responsible for the hypoxia-dependent induction of VEGF. When compared with normal lungs, SPH lungs showed decreased expression of the kinases PI3 kinase and sic, which, together with Akt, relay the signal transduction downstream of VEGFR-2. Because markers of angiogenesis are exp ressed in plexiform lesions in SPH, it is proposed that these lesions may f orm by a process of disordered angiogenesis. Copyright (C) 2001 John Wiley & Sons, Ltd.