Proteomics of transformed lymphocytes from a family with familial pulmonary arterial hypertension

Barbara O. Meyrick, David B. Friedman, D. Dean Billheimer, Joy D. Cogan, Melissa A. Prince, John A. Phillips, James E. Loyd

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Rationale: Not all family members with BMPR2 mutations develop pulmonary arterial hypertension (PAH), implying that additional modifier genes or proteins are necessary for full expression of the disease. Objectives: To determine whether protein expression is altered in patients with familial PAH (FPAH) compared with obligate carriers and nondiseased control subjects. Methods: Protein extractsfrom transformed blood lymphocytes from four patients with FPAH, three obligate carriers, and three marriedin control subjects from one family with a known BMPR2 mutation (exon 3 T354G) were labeled with either Cy3 or Cy5. Cy3/5 pairs were separated by standard two-dimensional differential gel electrophoresis using a Cy2-labeled internal standard of all patient samples. Log volume ratios were analyzed using a linear mixed effects model. Proteins were identified by matrix-assisted laser desorption ionization, time-of-flight mass spectrometry (MALDI-TOF MS) and tandem TOF/TOF MS/MS. Measurements and Main Results: Hierarchical clustering, heat-map, and principal components analysis revealed marked changes in protein expression in patients with FPAH when compared with obligate carriers. Significant changes were apparent in expression of 16 proteins (P<0.05) when affected patients were compared with obligates: nine showed a significant increase and seven showed a significant reduction. Conclusions: A series of novel proteins with altered expression were found that could distinguish affected patients from obligate carriers and married-in controls in a single family with a BMPR2 mutation. These differences provide new information highlighting proteins that may be involved in the mechanism(s) that differentiates those individuals with a BMPR2 mutation who develop FPAH from those who do not.

Original languageEnglish (US)
Pages (from-to)99-107
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Issue number1
StatePublished - Jan 1 2008


  • Catalytic activity
  • MALDI-TOF mass spectrometry
  • Obligate individuals without FPAH
  • Two-dimensional differential gel electrophoresis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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