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(Circulation Research. 2001;88:e2.)
© 2001 American Heart Association, Inc.

UltraRapid Communication

Microsatellite Instability of Endothelial Cell Growth and Apoptosis Genes Within Plexiform Lesions in Primary Pulmonary Hypertension

Michael E. Yeager, George R. Halley, Heiko A. Golpon, Norbert F. Voelkel, Rubin M. Tuder

From the Department of Pathology (M.E.Y., G.R.H., R.M.T.), University of Colorado Health Sciences Center, Denver, Colo; Pulmonary Hypertension Center and Division of Respiratory and Critical Care Sciences (H.A.G., N.F.V., R.M.T.), Department of Medicine, University of Colorado Health Sciences Center, Denver, Colo.

Correspondence to Rubin M. Tuder, MD, Department of Pathology, Box B216, University of Colorado Health Sciences Center, Denver, CO 80262. E-mail Rubin.Tuder{at}uchsc.edu

Abstract—Primary pulmonary hypertension (PPH) is a frequently fatal disease whose pathobiology is poorly understood. Monoclonal endothelial cell growth is present within plexiform lesions of patients with PPH but not secondary PH because of congenital heart malformations. We hypothesized that endothelial cells within PPH plexiform lesions harbor mutations permissive for clonal cell growth. We found that endothelial cells in PPH plexiform lesions demonstrated 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-ß receptor type II (6 of 19 lesions) and Bax (4 of 19 lesions). These results suggest that, in PPH, proliferated endothelial cells have genetic alterations associated with microsatellite instability and concomitant perturbation of growth and apoptosis gene expression akin to neoplasia. The full text of this article is available at http://www.circresaha.org.

Key Words: microsatellite instability • transforming growth factor-ß receptor type II • Bax • primary pulmonary hypertension

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