In vivo complex formation of oxidized alpha(1)-antitrypsin and LDL

Citation
S. Mashiba et al., In vivo complex formation of oxidized alpha(1)-antitrypsin and LDL, ART THROM V, 21(11), 2001, pp. 1801-1808
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
ISSN journal
1079-5642 → ACNP
Volume
21
Issue
11
Year of publication
2001
Pages
1801 - 1808
Database
ISI
SICI code
1079-5642(200111)21:11<1801:IVCFOO>2.0.ZU;2-U
Abstract
An inactivated form of at-antitrypsin (AT) and LDL coelutes in gel permeati on chromatography. To characterize and to quantify the amount of this fract ion of AT, a monoclonal antibody was established against chloramine T-oxidi zed AT and named OxAT-4. OxAT-4 recognized the oxidatively modified AT, inc luding hexylaldehyde- or 4-hydroxy-2-nonenal-modified AT, but neither norma l active AT nor trypsin/AT complex. Comigration of apoB and oxidized AT was demonstrated by Western blotting analysis of AT-LDL by means of anti-apoB monoclonal antibody and OxAT-4. A complex of oxidized AT and LDL (AT-LDL) w as isolated from human plasma LDL by affinity column with an OxAT-4 antibod y-coated carrier. AT-LDL was degraded 4 times more effectively by mouse per itoneal macrophages, but this was not mediated by scavenger receptor class A type I. Localization of AT-LDL was detected in human atherosclerotic lesi ons of the coronary artery, but distribution of it was not completely ident ical to that of macrophages. In situ hybridization revealed AT expression b y macrophages, which were present in intimal layers of the coronary artery. From these findings, we concluded that AT is produced and oxidized by macr ophages, then attached to LDL in the intimal layer of the arterial wall. Al though AT-LDL that escapes into the blood stream can be cleared by hepatocy tes, the remaining AT-LDL may be taken up by macrophages and contribute to the lipid accumulation in arterial wall cells as the early stage of atherog enesis.