Dysregulation of Calpain Proteolytic Systems Underlies Degenerative Vascular Disorders

by chronic inflammatory responses and accompanying reactive oxygen species (ROS)-mediated oxidative stress 7) ; thus, many researchers have tested anti-oxidative agents in clinical trials. Unfortunately, these antioxidative trials have thoroughly failed to reverse chronic vascular diseases 8) , although they were effective in acute inflammation, such as the acute phase of stroke 9) . Therefore, it is necessary to investigate how blood vessels shift toward degenerative status in chronic disease. In this regard, growing evidence suggests that the calpain proteolytic systems, comprised of Ca 2 -dependent intracellular proteases and a calpain endogenous inhibitor, critically contribute to degenerative vascular disorders. Calpains can be potentiated in the presence of pathophysiological stressors, such as inflammatory cytokines, growth factors, bioactive lipids and hypoxic stimulus As a result, dysregulation of these systems might be responsible for the vascular disorders noted above. In this review article, we discuss the current achievements in understanding the pathophysiology of degenerative vascular disorders, with a particular focus on the calpain proteolytic system.