Exosomal tetraspanins: the role of CD63 and CD81 in pathogenesis of myocardial infarction

Cardiovascular diseases are one of the major global health problems with high prevalence and mortality rates. Complex intercellular communications supported by circulating exosomes, recognized as important participants in the immunopathogenesis of atherosclerosis and coronary heart disease, thus playing a crucial role in pathogenesis and progression of cardiovascular diseases. Presuming tetraspanins (CD63 and CD81) being widely recognized as exosomal markers, the purpose of our study was to determine and evaluate the time dynamics of serum exosomal tetraspanins CD63 and CD81 production on 1st and 7th days after acute myocardial infarction. The study included 40 patients with acute myocardial infarction (AMI) aged 54.29±5.45 years and 10 healthy persons, matched for age and gender. Two types of tetraspanin dynamics were revealed following AMI in acute ischemic process in the myocardium. Type 1 is characterized by initially low values of tetraspanin CD63, compared to healthy individuals, and is accompanied by an increased production/release of exosomal CD63 on day 7; type 2 is characterized by higher CD63 values, exceeding reference values on day 1 after AMI, with its decrease by day 7. Our correlation analysis of tetraspanin CD63 allowed us to establish links with age, cholesterol, LDL, triglycerides and the number of platelets and leukocytes. The CD81 level in blood serum of AMI patients was significantly lower than in healthy individuals. The identified features of the production dynamics allowed us to classify patients by distinct response types: (1) with increase in serum exosomal CD81 and subsequent achievement of the target tetraspanin level typical for healthy individuals; (2) with a decreased concentration against initial level, associated with higher frequency of adverse cardiovascular events. The correlation analysis of serum CD81 allowed us to establish correlations with leukocyte counts, erythrocyte sedimentation rate and obesity grade. Exosomal profile of circulating CD63 and CD81 in individuals with AMI differs quantitatively from healthy subjects, being characterized by different types of dynamics of tetraspanin production during the first week of myocardial infarction.