Biomarkers and SNP-polymorphisms in Post-infarction Cardiac Remodeling
Condition: Myocardial Infarction
MeSH terms: Myocardial Infarction; Infarction
Study type: Observational

Summary: 
      The purpose of this study is to explore the serum levels of pro- and anti-inflammatory
      biomarkers and angiogenic growth factors and SNP polymorphisms of the promoter regions of
      their genes as well as to determine their role in the development of adverse cardiac
      remodeling in patients with acute ST-segment elevation myocardial infarction.
    

Detailed description: 
      The widespread introduction of modern methods of treatments of myocardial infarction in
      routine clinical practice has lead not only to a decrease in mortality, but also to an
      increase in the number of patients with chronic heart failure. It is known that inflammation
      develops in myocardial infarction in response to cell damage, which is accompanied by
      activation of the cells of the immune system and eventually with scarring. Chronic aseptic
      inflammation is not only a universal biological reaction in response to necrosis of
      cardiomyocytes, but the cellular molecular basis of post-infarction cardiac remodeling. At
      the same time, the imbalance of pro- and anti-inflammatory mediators can have some negative
      effects on the healing processes of the damaged myocardium and subsequent remodeling of the
      heart. In adverse heart remodeling, elevated levels of proinflammatory cytokines (IL-1β,
      IL-6, TNF-α, etc.) and reduced secretion of anti-inflammatory cytokines (IL-4, IL-10, etc.)
      persist for a long time.

      Recently, the endotoxin hypothesis of cytokine production has been of great interest among
      scientists. Endotoxin is a molecule of the lipopolysaccharide (LPS) of the outer cell wall of
      gram-negative bacteria. LPS is a powerful inducer of cytokine release, and chronic endotoxin
      load is at least one of the reasons for the activation of the innate immune system. One of
      the most important and unresolved problems in pathophysiology is the study of the nature of
      the inflammatory response, or rather the cytokine response cascade, reparation and
      neoangiogenesis developing in the myocardium in response to ischemic damage, as well as
      genetically determined regulation of these processes. Factors determining the dual role of
      cytokines in the development of adverse cardiac remodeling can be polymorphisms of their
      genes, in particular, single nucleotide polymorphism of genes - SNP (single nucleotide
      polymorphism) with replacement of one nucleotide by another. SNP in promoter regions regulate
      the intensity of gene expression, different levels of secretion and function of interleukins,
      growth factors, and, accordingly, their biological effects. Uncovering the mechanisms that
      regulate the secretion of angiogenic growths factors, pro- and anti-inflammatory cytokines in
      patients with AMI could potentially become the basis for developing new treatment tactics
      based on modulating the immune response and neoangiogenesis in AMI by introducing into
      ischemic tissues of cytokines or angiogenic growth factors in the form recombinant proteins
      or as a part of genetic constructs to stimulate regeneration.

      A total of 200 patients with acute primary myocardial infarction with ST segment elevation
      will be recruited. Upon admission, all patients receive standard therapy, as recommended for
      the treatment of myocardial infarction. Within 24 hours of admission, coronary angiography
      and revascularization of the infarct-related artery are performed. On the days 1 and 7 of
      hospitalization and on the day of discharge, blood will be taken to determine the dynamics of
      serum concentrations of pro- and anti-inflammatory biomarkers, markers of myocardial
      necrosis; gene polymorphisms will be studied; echocardiography will be performed to assess
      the structural and functional characteristics of the heart after AMI. After 3 and 12 months,
      patients undergo studies to dynamically assess the structural and functional state of the
      heart.
    

Intervention name(s): SNP polymorphisms of the promoter regions pro - and anti-inflammatory cytokines and angiogenic growth factor
Intervention type(s): Genetic
Intervention description(s): blood sampling
Intervention MeSH terms: Anti-Inflammatory Agents; Mitogens
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with acute myocardial infarction with ST segment elevation, who underwent coronary
        angiography within 24 hours of the onset of the disease.
      
Biospecimen description: 
      Samples will be obtained from patients with acute ST segment elevation myocardial infarction,
      who underwent coronary angiography within 24 hours of the onset of the disease.
    
Keywords: remodeling; inflammation; polymorphism; endotoxin; heart failure