Abstract
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 language | English (US) |
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Pages (from-to) | 99-107 |
Number of pages | 9 |
Journal | American journal of respiratory and critical care medicine |
Volume | 177 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2008 |
Externally published | Yes |
Keywords
- 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