Calpain and Atherosclerosis
スポンサーリンク
概要
- 論文の詳細を見る
This review highlights the pro-atherogenic roles of Ca2+-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.
- 一般社団法人 日本動脈硬化学会の論文
一般社団法人 日本動脈硬化学会 | 論文
- Effects of Lysosomal Protease Inhibitors on the Degradation of Acetylated Low Density Lipoprotein in Cultured Rat Peritoneal Macrophages
- Genomic Structure and Mapping of Human Orphan Receptor LXR Alpha : Upregulation of LXRa mRNA During Monocyte to Macrophage Differentiation
- The Gene Expression Profile of Human Umbilical Vein Endothelial Cells Stimulated by Tumor Necrosis Factor a Using DNA Microarray Analysis
- Participation of T Lymphocytes and Macrophages in Atherogenesis
- Immunohistochemical and Quantitative Analysis of Cellular and Extracellular Components of Aortic Atherosclerosis in WHHL Rabbits