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Cardiovascular disease is a major cause of mortality and morbidity. Every year, about 37 million people throughout the world die of cardiovascular diseases. Cardiovascular disease is mainly caused by a blockage that prevents blood from flowing to heart or the brain. The most common reason for blockage is a build-up of fatty deposits, inflammation and atherosclerotic plaques on the inner walls of blood vessels. It is assumed that cardiovascular disease related proteins will be released from the deposits or plaque on the inner wall of blood vessels. If it is possible to monitor the increase or decrease of these proteins, the incident of cardiovascular disease will be prevented. Proteomics is a powerful tool to describe changes in protein expression. In the present study, to identify the changed proteins for diagnosis of cardiovascular disease, protein profiles of human sera 20 of non-diabetic cardiovascular disease patients were compared with those of 30 healthy controls by using the two-dimensional gel electrophoresis technique. And the cardiovascular disease was induced in compliance with a diabetic complication. In order to except diabetic complication, cardiovascular disease patients with a diabetic complication (n=30) were compared with healthy controls (n=30) by using two-dimensional gel electrophoresis. As the results, the differentially expressed spots in cardiovascular disease patients were identified with ESI-Q-TOF (electrospray ionization quadrupole time-of-flight) mass spectrometry. Among the identified proteins, A and B were confirmed to be a good candidates as biomarkers for cardiovascular disease. This result suggests that the A and B proteins can be used as diagnostic and monitoring biomarkers of cardiovascular disease if further studies are done.