Microsatellite instability of endothelial cell growth and apoptosis genes within plexiform lesions in primary pulmonary hypertension

Primary pulmonary hypertension (PPH) is a frequently fatal disease whose pa thobiology is poorly understood. Monoclonal endothelial cell growth is pres ent within plexiform lesions of patients with PPH but not secondary PH beca use of congenital heart malformations. We hypothesized that endothelial cel ls within PPH plexiform lesions harbor mutations permissive for clonal cell growth. We found that endothelial cells in PPH plexiform lesions demonstra ted microsatellite instability within the human MutS Homolog 2 gene (10 of 20 lesions) and displayed microsatellite site mutations and reduced protein expression of transforming growth factor-beta receptor type II (6 of 19 le sions) and Bax (4 of 19 lesions). These results suggest that, in PPH, proli ferated endothelial cells have genetic alterations associated with microsat ellite instability and concomitant perturbation of growth and apoptosis gen e expression akin to neoplasia. The full text of this article is available at http://www.circresaha.org.