title: The human HDL proteome displays high inter-individual variability and is altered dynamically in response to angioplasty-induced atheroma plaque rupture.
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.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Jorge
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain; Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón, I+CS, Zaragoza, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Burillo
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Mesa
authors.affiliation: Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón, I+CS, Zaragoza, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Baila-Rueda
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
authors.forename: Margoth
authors.initials: M
authors.lastname: Moreno
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Marco
authors.initials: M
authors.lastname: Trevisan-Herraz
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Silla-Castro
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Camafeita
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Ortega-Muñoz
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Bonzon-Kulichenko
authors.affiliation: Hospital Universitario Miguel Servet, Servicio de Cardiología, Zaragoza, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Calvo
authors.affiliation: Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón, I+CS, Zaragoza, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Cenarro
authors.affiliation: Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón, I+CS, Zaragoza, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Civeira
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. Electronic address: jvazquez@cnic.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Vázquez
mesh_terms: D000465:Algorithms; D001053:Apolipoproteins / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D002846:Chromatography, Affinity; D002853:Chromatography, Liquid; D003324:Coronary Artery Disease / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007525:Isoelectric Focusing; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008297:Male; D010455:Peptides / Q000737:chemistry; D058226:Plaque, Atherosclerotic / Q000378:metabolism*; D020543:Proteome; D040901:Proteomics; D015203:Reproducibility of Results; D049490:Systems Biology; D053719:Tandem Mass Spectrometry; D014357:Trypsin / Q000737:chemistry
chemical_list: D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D010455:Peptides; D020543:Proteome; D002784:Cholesterol; D014357:Trypsin
keywords: Atheroma plaque; HDL; Proteomics; Stable isotopic labeling; System biology