Alpha-1-antitrypsin in Plasma Exosomes and Pericardial Fluid Exosomes Are Associated With Severity of Rheumatic Heart Disease

Rheumatic heart is an autoimmune sequel of pharyngitis and rheumatic fever that leads to permanent heart valves damage, especially the mitral valves. The mitral valves, which are responsible for the binding of auto-antibodies during immune response generation, leads to valves scarring and eventually mitral valve dysfunction. Recently, exosomes (EXOs), the nano-sized-vesicles, which ranges in size from 30-150 nm, are involved in various cardiovascular physiological and pathological processes. These vesicles are found in several body fluids such as plasma, serum and also in cell culture media. Exosomal cargo contains proteins, which are taken up by the recipient cells and modulates the cellular characteristics. The role of exosomal proteins in RHD is still obscure. Hence, the present study is designed to unveil the role of exosomal proteins in increasing disease severity during RHD. In this study, the exosomes were isolated from biological fluids (plasma and pericardial fluid) of RHD patients as well as from their respective controls. Protein profiling of these isolated exosomes revealed that alpha-1 antitrypsin is up-regulated in the biological fluids of RHD patients. The augmented levels of exosomal alpha-1 antitrypsin, was further, validated in biological samples and mitral valve tissues of RHD patients, which was further correlated with the disease severity. These findings suggest that increased levels of exosomal alpha-1 antitrypsin is responsible for increased severity during RHD.