Identification of altered plasma proteins by proteomic study in valvular heart diseases and the potential clinical significance

PLoS One. 2013 Aug 27;8(8):e72111. doi: 10.1371/journal.pone.0072111. eCollection 2013.

Abstract

Background: Little is known about genetic basis and proteomics in valvular heart disease (VHD) including rheumatic (RVD) and degenerative (DVD) valvular disease. The present proteomic study examined the hypothesis that certain proteins may be associated with the pathological changes in the plasma of VHD patients.

Methods and results: Differential protein analysis in the plasma identified 18 differentially expressed protein spots and 14 corresponding proteins or polypeptides by two-dimensional electrophoresis and mass spectrometry in 120 subjects. Two up-regulated (complement C4A and carbonic anhydrase 1) and three down-regulated proteins (serotransferrin, alpha-1-antichymotrypsin, and vitronectin) were validated by ELISA in enlarging samples. The plasma levels (n = 40 for each) of complement C4A in RVD (715.8±35.6 vs. 594.7±28.2 ng/ml, P = 0.009) and carbonic anhydrase 1 (237.70±15.7 vs. 184.7±10.8 U/L, P = 0.007) in DVD patients were significantly higher and that of serotransferrin (2.36±0.20 vs. 2.93±0.16 mg/ml, P = 0.025) and alpha-1-antichymotrypsin (370.0±13.7 vs. 413.0±11.6 µg/ml, P = 0.019) in RVD patients were significantly lower than those in controls. The plasma vitronectin level in both RVD (281.3±11.0 vs. 323.2±10.0 µg/ml, P = 0.006) and DVD (283.6±11.4 vs. 323.2±10.0 µg/ml, P = 0.011) was significantly lower than those in normal controls.

Conclusions: We have for the first time identified alterations of 14 differential proteins or polypeptides in the plasma of patients with various VHD. The elevation of plasma complement C4A in RVD and carbonic anhydrase 1 in DVD and the decrease of serotransferrin and alpha-1-antichymotrypsin in RVD patients may be useful biomarkers for these valvular diseases. The decreased plasma level of vitronectin - a protein related to the formation of valvular structure - in both RVD and DVD patients might indicate the possible genetic deficiency in these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Blood Proteins / metabolism*
  • Case-Control Studies
  • Down-Regulation
  • Female
  • Heart Valve Diseases / blood*
  • Humans
  • Male
  • Middle Aged
  • Proteomics
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Up-Regulation

Substances

  • Biomarkers
  • Blood Proteins

Grant support

The work described in this paper was fully supported by grants from the National Natural Science Foundation of China (No. 81170148), the National Basic Research Program of China (No. 2010CB529500), International S & T Cooperation Program of China (No. 2009DFB30560) and Tianjin Municipal Science and Technology Commission 09ZCZDSF04200 and 10JCYBJC26400, Tianjin Municipal Research Grant for Applied Basic and Frontier Technology, China, Binhai Key Platform for Creative Research Program (2012-BH110004), Tianjin Binhai New Area Health Bureau (2011BHKZ001 and 2012BWKZ 008) and (2011BHKY002 and 2012 BWKY024) Tianjin Health Bureau (2012KZ009 and 2012KZ010), and Hong Kong Research Grants Council Grants (CUHK4789/09). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.