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J Proteomics. 2014 Jun 25;106:61-73. doi: 10.1016/j.jprot.2014.04.010. Epub 2014 Apr 18.

The human HDL proteome displays high inter-individual variability and is altered dynamically in response to angioplasty-induced atheroma plaque rupture.

Author information

1
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
2
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain; Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón, I+CS, Zaragoza, Spain.
3
Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón, I+CS, Zaragoza, Spain.
4
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
5
Hospital Universitario Miguel Servet, Servicio de Cardiología, Zaragoza, Spain.
6
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. Electronic address: jvazquez@cnic.es.

Abstract

Recent findings support potential roles for HDL in cardiovascular pathophysiology not related to lipid metabolism. We address whether HDL proteome is dynamically altered in atheroma plaque rupture. We used immunoaffinity purification of HDL samples from coronary artery disease patients before and after percutaneous transluminal coronary angioplasty (PTCA), a model of atheroma plaque disruption. Samples were analyzed by quantitative proteomics using stable isotope labeling and results were subjected to statistical analysis of protein variance using a novel algorithm. We observed high protein variability in HDL composition between individuals, indicating that HDL protein composition is highly patient-specific. However, intra-individual protein variances remained at low levels, confirming the reproducibility of the method used for HDL isolation and protein quantification. A systems biology analysis of HDL protein alterations induced by PTCA revealed an increase in two protein clusters that included several apolipoproteins, fibrinogen-like protein 1 and other intracellular proteins, and a decrease in antithrombin-III, annexin A1 and several immunoglobulins. Our results support the concept of HDL as dynamic platforms that donate and receive a variety of molecules and provide an improved methodology to use HDL proteome for the systematic analysis of differences among individuals and the search for cardiovascular biomarkers. Biological significance The HDL proteome is an interesting model of clinical relevance and has been previously described to be dynamically altered in response to pathophysiological conditions and cardiovascular diseases. Our study suggests that interindividual variability of HDL proteome is higher than previously thought and provided the detection of a set of proteins that changed their abundance in response to plaque rupture, supporting the concept of HDL as dynamic platforms that donate and receive a variety of molecules.

KEYWORDS:

Atheroma plaque; HDL; Proteomics; Stable isotopic labeling; System biology

PMID:
24747125
DOI:
10.1016/j.jprot.2014.04.010
[Indexed for MEDLINE]

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