title: Calpain and atherosclerosis.
abstract: This review highlights the pro-atherogenic roles of Ca(2+)-sensitive intracellular protease calpains. Among more than ten species of calpain isozymes, µ- and m-calpains have been characterized most extensively. These two isozymes are ubiquitously expressed in mammalian tissues, including blood vessels, and tightly regulate functional molecules in the vascular component cells through limited proteolytic cleavage. Indeed, previous cell-based experiments showed that calpains play significant roles in nitric oxide production in vascular endothelial cells (ECs), maintenance of EC barrier function and angiogenesis for maintaining vascular homeostasis. Recently, we demonstrated that modified-low density lipoprotein (LDL)-induced m-calpain causes hyperpermeability in ECs, leading to the infiltration of monocytes/macrophages and plasma lipids into the intimal spaces (Miyazaki T. et al., Circulation. 2011; 124: 2522-2532). Calpains also mediate oxidized LDL-induced apoptotic death in ECs. In monocytes/macrophages, calpains induce proteolytic degradation of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1), which results in impaired cholesterol efflux and subsequent macrophage foam cell formation. In vascular smooth muscle cells, calpains may be involved in the conversion from contractile phenotype to proliferative phenotype. In hepatocytes, calpains disrupt the biogenesis of high-density lipoprotein via proteolytic degradation of ABCA1. Thus, calpains may serve as novel candidate molecular targets for control of atherosclerosis.
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, Tokyo 142-8555, Japan. taku@pharm.showa-u.ac.jp
authors.forename: Takuro
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Koya
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Kigawa
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Oguchi
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Lei
authors.forename: Joo-ri
authors.initials: JR
authors.lastname: Kim-Kaneyama
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazaki
mesh_terms: D050197:Atherosclerosis / Q000503:physiopathology*; D002154:Calpain / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000166:cytology; D009000:Monocytes / Q000166:cytology
chemical_list: D002154:Calpain