Angiogenic Growth Factors, Pro- and Anti-inflammatory Biomarkers, and Genetic Polymorphisms of Their Promoter Regions in Patients With Post-infarction Cardiac Remodeling

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.