Proteomic study of plasma from moderate hypercholesterolemic patients

被引:38
作者
Alonso-Orgaz, Sergio
Moreno, Laura
Macaya, Carlos
Rico, Luis
Mateos-Caceres, Petra J.
Sacristan, Daniel
Perez-Vizcaino, Francisco
Segura, Antonio
Tamargo, Juan
Lopez-Farre, Antonio
机构
[1] Hosp Clin San Carlos, Cardiovasc Inst, Dept Cardiol, Cardiovasc Res Unit, Madrid 28040, Spain
[2] Univ Complutense Madrid, Sch Med, Dept Pharmacol, E-28040 Madrid, Spain
[3] Fdn Jimenez Diaz, Dept Internal Med, E-28040 Madrid, Spain
[4] Hlth Sci Inst, Talavera Reina, Toledo, Spain
关键词
hypercholesterolemia; plasma proteins; proteomics; simvastatin;
D O I
10.1021/pr060159w
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Proteomics is a technology to detect and identify several proteins and their isoforms in a single sample. We used proteomics to analyze modifications in the protein map of plasma after simvastatin treatment of moderate hypercholesterolemic patients. Plasma from hypercholesterolemic patients (n = 9) was compared before and after 12 weeks of simvastatin treatment ( 40 mg/day). Patients with similar cardiovascular risk factors were used as controls (CR group). By using two-dimensional electrophoresis and mass spectrometry, we identified the different protein isoforms. The plasma expression of three fibrinogen gamma chain isoforms (FGG) was enhanced, whereas the expression of two isoforms of the fibrinogen beta chain (FGB) was reduced in the hypercholesterolemic patients compared with the CR group. The expression of apolipoprotein A-IV and three haptoglobin isoforms was higher in hypercholesterolemic patients. Simvastatin treatment modified the plasma expression of FGG chain isoform 1, FGB chain isoforms 1 and 2, vitamin D binding protein isoform 3, apo A-IV, and haptoglobin isoform 2. The modification of FGG chain isoform 1 and FGB chain isoforms 1 and 2 was positively correlated with total plasma cholesterol level. Proteomic analysis of plasma may help to know more in depth the molecular mechanism modified by simvastatin treatment.
引用
收藏
页码:2301 / 2308
页数:8
相关论文
共 46 条
  • [1] Cholesterol lowering and coronary artery disease: mechanisms of risk reduction
    Archbold, RA
    Timmis, AD
    [J]. HEART, 1998, 80 (06) : 543 - 547
  • [2] Simvastatin inhibits expression of tissue factor in advanced atherosclerotic lesions of apolipoprotein E deficient mice independently of lipid lowering: potential role of simvastatin-mediated inhibition of Egr-1 expression and activation
    Bea, F
    Blessing, E
    Shelley, MI
    Shultz, JM
    Rosenfeld, ME
    [J]. ATHEROSCLEROSIS, 2003, 167 (02) : 187 - 194
  • [3] APPARENT HYDROXYL RADICAL PRODUCTION BY PEROXYNITRITE - IMPLICATIONS FOR ENDOTHELIAL INJURY FROM NITRIC-OXIDE AND SUPEROXIDE
    BECKMAN, JS
    BECKMAN, TW
    CHEN, J
    MARSHALL, PA
    FREEMAN, BA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (04) : 1620 - 1624
  • [4] INTERACTION OF THE VITAMIN D-BINDING PROTEIN (GROUP-SPECIFIC COMPONENT) AND ITS LIGAND 25-HYDROXY-VITAMIN-D3 - BINDING DIFFERENCES OF THE VARIOUS GENETIC TYPES DISCLOSED BY ISOELECTRIC-FOCUSING
    BRAUN, A
    BRANDHOFER, A
    CLEVE, H
    [J]. ELECTROPHORESIS, 1990, 11 (06) : 478 - 483
  • [5] New insights into the pharmacodynamic and pharmacokinetic properties of statins
    Corsini, A
    Bellosta, S
    Baetta, R
    Fumagalli, R
    Paoletti, R
    Bernini, F
    [J]. PHARMACOLOGY & THERAPEUTICS, 1999, 84 (03) : 413 - 428
  • [6] Iron status and risk of cardiovascular disease
    Corti, MC
    Gaziano, M
    Hennekens, CH
    [J]. ANNALS OF EPIDEMIOLOGY, 1997, 7 (01) : 62 - 68
  • [7] Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease - Meta-analyses of prospective studies
    Danesh, J
    Collins, R
    Appleby, P
    Peto, R
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1998, 279 (18): : 1477 - 1482
  • [8] Beneficial cardiovascular pleiotropic effects of statins
    Davignon, J
    [J]. CIRCULATION, 2004, 109 (23) : 39 - 43
  • [9] Haptoglobin polymorphism, a genetic risk factor in coronary artery bypass surgery
    Delanghe, J
    Cambier, B
    Langlois, M
    DeBuyzere, M
    Neels, H
    DeBacquer, D
    VanCauwelaert, P
    [J]. ATHEROSCLEROSIS, 1997, 132 (02) : 215 - 219
  • [10] Haptoglobin polymorphism and peripheral arterial occlusive disease
    Delanghe, J
    Langlois, M
    Duprez, D
    De Buyzere, M
    Clement, D
    [J]. ATHEROSCLEROSIS, 1999, 145 (02) : 287 - 292