Autophagy Activity in Epicardial Cells in Acute Pericarditis

Abstract

Pericarditis is a group of polyetiological diseases often associated with emergence of life– threatening conditions. Poor knowledge of underlying cellular mechanisms and lack of relevant approaches to investigation of pericarditis result in major challenges in diagnosis and treatment.The aim of this work was to identify changes in the activity of autophagy in epicardial cells in acute pericarditis.Materials and methods. Acute pericarditis in mice was induced by intrapericardial injection of Freund's adjuvant in the study group (n=15). The control group included animals receiving either intrapericardial injection of phosphate-buffered saline (PBS) (n=15), or sham surgery without injections (n=7). On Days 3 or 5 after surgery the animals were euthanized under isoflurane anesthesia. Immunofluorescence staining of cardiac tissue cryo-sections and immunoblotting were used to assess the intensity of inflammation and autophagy in the epicardium.Results. Inflammation and other signs of acute pericarditis resulting in thickening of some epicardial areas were found: 68+9% in the control (after PBS injection) and 124+22% after Freund's adjuvant injection (p=0.009); other signs included cellular infiltration of epicardium and multiple adhesions. The epicardial layer exhibited signs of mesothelial cells reorganization with 11-fold increase of autophagy markers LC3 II/LC3 I ratio: 0.07+0.02 in the control group (after PBS injection) and 0.84+0.07 - in acute pericarditis (p=0.04), and accumulation of collagen fibers.Conclusion. Development of acute pericarditis is accompanied by activation of epicardial mesothelial cells, intensified autophagy and development of fibrous changes in epicacardial/ subepicardial areas.