Macrophage Phenotype in Type 2 Diabetics After Myocardial Infarction and the Potential Role of miRNAs Secreted
Condition: DIABETES; MYOCARD INFARCTUS
MeSH terms: Myocardial Infarction; Infarction
Study type: Interventional

Summary: 
      The prevalence of type 2 diabetes is growing steadily. Patients with diabetes, cardiovascular
      complications (such as myocardial infarction (MI)) are more frequent and severe than in
      non-diabetic subjects. The anti-diabetic therapies available have little or no effect on the
      incidence of cardiovascular events. It is therefore urgent in diabetics develop new
      therapeutic strategies to reduce the occurrence of MI or limit the consequences.

      In the two weeks following MI, monocytes / macrophages are the most represented in the
      ischemic heart tissue cells. The infiltration by monocytes / macrophages after infarction MI
      is a two-phase process. In the first phase, monocytes / macrophages M1 promote digestion
      injured areas, and monocytes / macrophages M2 intervene to promote angiogenesis, collagen
      deposition and contribute to tissue repair. The optimal repair after myocardial infarction
      depends on effective recruitment of monocytes and macrophages M1 transition needed to digest
      the damaged tissue and M2 macrophages necessary for tissue repair. The balance between these
      two phenotypes M1 and M2 is controlled by different modulators, such as transcription
      factors, cellular miRNA and miRNA extracellular contained in the microvesicles (MVs).
      Interestingly, plasma MVs circulating essentially derived monocytes and platelets contain
      miRNA and are impaired by inflammation or during various pathological situations (such as
      IDM). Furthermore, metabolic disorders such as hypercholesterolemia (often associated with
      diabetes) affect the transition from M1 to M2 response and response delay cardiac repair. To
      date, the mechanisms that control the M1 / M2 transition at heart level are not elucidated.
      Moreover, the impact of diabetes, which leads to chronic low-grade inflammation, is not
      explored. Targeting the immune response by promoting the transition M1 / M2 after MI could be
      an innovative therapeutic approach. However, better characterization of the response of M1
      and M2 macrophages after MI and the mechanisms by which they contribute to tissue remodeling
      and the effect of diabetes are needed. The goal is to study how the phenotypes / macrophage
      functions after MI are changed by diabetes and to determine the potential role of miRNAs
      contained in secreted MVs in the transition M1 / M2 after MI.

      Monocytes / macrophages from subjects with normal blood sugar or diabetes who underwent an
      IDM (10 per group) will be characterized phenotypically. Their ability to produce MVs will be
      analyzed. These MVs will be tested functionally for their ability to orient the polarization
      of healthy recipients monocytes. The content of these MVs in terms of miRNAs will be analyzed
      in detail. By bioinformatics analysis, some miRNAs of interest (based on their abundance and
      target genes) will be selected. These miRNAs are over-expressed in macrophages and MVs
      produced by these cells will be analyzed for their ability to modulate differentiation of
      monocytes recipients. Finally, the circulating levels of these miRNAs of interest will be
      measured after 1 year of IDM and will be correlated to the clinical phenotype of patients
      (recurrence, arrhythmias, heart failure). Ultimately, the goal is to identify VMs that can
      promote the differentiation of monocytes to an alternative phenotype and identify miRNAs
      responsible for this effect. This could help in the future, in a subject with impaired
      ability of monocytes to differentiate alternatively, can change by introducing the miRNA of
      interest to re-inject or inject MVs macrophage containing the miRNA of interest and thus
      correct the defect of differentiation.
    


Intervention name(s): blood sample
Intervention type(s): Procedure
Intervention description(s): blodd sample at 12 months
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science