Discovery of New Circulating Biomarkers of Coronary Atherosclerosis
Condition: Coronary Artery Disease; Acute Coronary Syndromes; Myocardial Infarction; Atherosclerosis
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Myocardial Infarction; Acute Coronary Syndrome; Atherosclerosis; Infarction
Study type: Observational

Summary: 
      The study hypothesis is that differential proteomic techniques can be used to discover new
      circulating biomarkers of coronary atherosclerosis in the blood of patients suffering from
      coronary artery disease (either stable or unstable) who will be compared to a group of
      patients without coronary artery disease
    

Detailed description: 
      Hypothesis: Our hypothesis is that coronary atherosclerosis induces both quantitative and
      qualitative modifications of circulating proteins, which can be captured by a differential
      proteomic approach applied to serum or plasma samples. Identification of such modifications
      in the circulating blood of patients with coronary artery disease (versus patients without
      coronary artery disease) and/or of patients with acute coronary syndromes (versus stable
      coronary artery disease) may lead to discovery of new biomarkers of coronary atherosclerosis
      and of atherosclerotic plaque vulnerability.

      Objectives:

      Primary objective: Identification of new circulating biomarkers of stable and unstable
      coronary artery disease using a new approach of differential proteomics.

      Secondary objectives:

        -  Evaluation of the diagnostic value of these new biomarkers for the diagnosis of stable
           and unstable coronary artery disease.

        -  Comparison of the diagnostic value of these new biomarkers to the diagnostic value of 1)
           other validated biomarkers of atherosclerosis (eg, CRP, IL-6, CD40L, markers of
           leukocyte activation, …); and 2) of non-invasive measures of arterial function (eg,
           carotid artery intima-media thickness, pulse wave velocity, ankle/brachial index, …)

        -  Description of the relationship between these new biomarkers and major adverse coronary
           events (death, myocardial infarction, revascularization) during a 12-month follow-up.

      Methods:

      Uniq center, prospective study. Three groups of patients will be studied. Group 1:
      Non-ST-elevation acute myocardial infarction; Group 2: Stable coronary artery disease; Group
      3: normal coronary arteries and absence of other detectable atherosclerotic lesions.

      A new proteomic approach will be applied to serum and plasma samples obtained 1 month after
      the index hospitalisation. This approach includes 3 steps: 1) equalisation of circulating
      proteins (expose low-concentration proteins belonging to the "deep-proteome"); 2) Retention
      chromatography; and 3) protein separation using 2D-electrophoresis and Surface-Enhanced Laser
      Desorption/Ionisation Time-of-Flight (SELDI-TOF).

      Biomarkers with the highest diagnostic value will be subsequently identified using
      Matrix-Assisted Laser Desorbtion/Ionisation Time-of-Flight (MALDI-TOF) and tandem mass
      spectrometry (MS/MS).

      Perspectives:

      Validation of the diagnostic and prognostic values of the new biomarkers discovered and
      identified using the proteomic approach described above will require development of more
      straightforward measurement techniques (eg, ELISA), which will be used prospectively or
      retrospectively in other cohorts of patients with coronary artery disease. Basic studies will
      be performed in parallel, so as to better understand the role of these new biomarkers in the
      pathophysiology of atherosclerosis.
    

Intervention name(s): per intervention
Intervention type(s): Procedure
Intervention description(s): per intervention
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Identification de nouveaux marqueurs circulants de l'athérosclérose coronarienne et de ses
        complications par une nouvelle technique de protéomique différentielle.

        Identification of new parqueurs circulated in coronary artheriosclerosis and complications
        of the new differentiel technicology
      
Biospecimen description: 
      biomarqueurs
    
Keywords: Biomarkers; Proteomics; Mass spectrometry; Atherosclerosis; Acute coronary syndromes; Myocardial infarction; Coronary artery disease