title: Changes in the heparin affinity of extracellular-superoxide dismutase in patients with coronary artery atherosclerosis.
abstract: Extracellular-superoxide dismutase [EC 1.15.1.1] (EC-SOD) is a secretory glycoprotein with high affinity for heparin. This enzyme locates in blood vessel walls at a high enough level to suppress oxidative stress under normal conditions. EC-SOD is the major SOD isozyme in plasma, anchored to heparan sulfate proteoglycans in the glycocalyx of endothelial cell surfaces. Plasma EC-SOD is heterogeneous in heparin affinity and can be divided into five fractions, I to V, by heparin-HPLC. It has been suggested that EC-SOD form V is the primary form synthesized in the body and that EC-SOD forms with reduced heparin affinity are the result of proteolytic truncation of the C-terminal end of EC-SOD form V which is responsible for the binding with heparin. Recently, we reported that only plasma EC-SOD form V, with the highest heparin affinity, was increased by intravenous injection of heparin. The heparin affinity of plasma EC-SOD in patients with coronary atherosclerosis (CA+ patients) was compared in this study. The increase of plasma EC-SOD form V after heparin injection in CA+ patients was significantly less than that in subjects without evidence of stenosis in their major coronary arteries (CA- subjects). On the other hand, in CA+ patients, EC-SOD forms I to III, with low heparin affinity, were significantly increased compared to those in CA- subjects. EC-SOD in plasma apparently forms an equilibrium between the plasma phase and endothelial cell surface, and EC-SOD on the endothelial cell surface contributes to protecting the vessel wall against oxidative stress. These findings suggest that the quantitative and qualitative changes of EC-SOD, i.e., the decrease of bound EC-SOD on the endothelial cell surface, might suppress the defense systems against oxidative stress, which causes in part the development of coronary artery atherosclerosis.
authors.affiliation: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Adachi
authors.forename: N
authors.initials: N
authors.lastname: Yamazaki
authors.forename: H
authors.initials: H
authors.lastname: Tasaki
authors.forename: T
authors.initials: T
authors.lastname: Toyokawa
authors.forename: K
authors.initials: K
authors.lastname: Yamashita
authors.forename: K
authors.initials: K
authors.lastname: Hirano
mesh_terms: D000368:Aged; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000473:pathology; D018450:Disease Progression; D005110:Extracellular Space / Q000201:enzymology; D005260:Female; D006493:Heparin / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000097:blood* / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D013482:Superoxide Dismutase / Q000097:blood* / Q000187:drug effects*
chemical_list: D007527:Isoenzymes; D006493:Heparin; D013482:Superoxide Dismutase