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

Circ Res. 2001 Jan 19;88(1):E2-E11. doi: 10.1161/01.res.88.1.e2.


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-beta 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / genetics
  • Base Sequence
  • Cell Division / genetics
  • Cell Line
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Humans
  • Hypertension, Pulmonary / genetics*
  • Hypertension, Pulmonary / pathology
  • Microsatellite Repeats / genetics*
  • Mutation
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-bcl-2*
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics*
  • Tumor Cells, Cultured
  • bcl-2-Associated X Protein


  • BAX protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Transforming Growth Factor beta
  • bcl-2-Associated X Protein
  • DNA
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II