Inhibition of endothelial cell thromboresistance by homocysteine

被引:30
作者
Ling, Q
Hajjar, KA [1 ]
机构
[1] Cornell Univ, Weill Med Coll, Dept Pediat, New York, NY 10021 USA
[2] Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA
关键词
homocysteine elongation factors; endothelial cell; tissue plasminogen activator; plasmin;
D O I
10.1093/jn/130.2.373S
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Homocysteine (HC) is a highly reactive thiol intermediate in amino acid metabolism, which can modify the function of endothelial cells in a myriad of ways. In vitro, homocysteine can inhibit the thromboresistance properties of the endothelial cell by induction of procoagulant factors, inactivation of natural anticoagulant systems, and suppression of vasodilatory and platelet-modulating factors. HC also inhibits the fibrinolytic system by impairing the ability of the endothelial cell to bind tissue plasminogen activator (t-PA), by interacting directly with the t-PA binding "tail" domain of its endothelial cell receptor, annexin II. Moreover, HC influences endothelial cell gene expression as exemplified by induction of the elongation factor-1. family of polypeptides, which promote polypeptide chain elongation during mRNA translation. Induction of EF-1 subunits alpha, beta, gamma and delta by homocysteine is associated with increased turnover of at least one free thiol-containing protein, suggesting that up-regulation of these subunits may represent a mechanism for replacement of damaged or modified proteins. A more complete understanding of the diverse effects of homocysteine on endothelial cell function may provide important clues to the precise role homocysteine may play in the initiation and progression of vascular disease.
引用
收藏
页码:373S / 376S
页数:4
相关论文
共 31 条
[1]  
CESARMAN GM, 1994, J BIOL CHEM, V269, P21198
[2]   Induction of acute translational response genes by homocysteine -: Elongation factors-1α, -β, and -δ [J].
Chacko, G ;
Ling, Q ;
Hajjar, KA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (31) :19840-19846
[3]   ABNORMALLY HIGH THROMBOXANE BIOSYNTHESIS IN HOMOZYGOUS HOMOCYSTINURIA - EVIDENCE FOR PLATELET INVOLVEMENT AND PROBUCOL-SENSITIVE MECHANISM [J].
DIMINNO, G ;
DAVI, G ;
MARGAGLIONE, M ;
CIRILLO, F ;
GRANDONE, E ;
CIABATTONI, G ;
CATALANO, I ;
STRISCIUGLIO, P ;
ANDRIA, G ;
PATRONO, C ;
MANCINI, M .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (03) :1400-1406
[4]   HOMOCYSTEINE, A RISK FACTOR FOR PREMATURE VASCULAR-DISEASE AND THROMBOSIS, INDUCES TISSUE FACTOR ACTIVITY IN ENDOTHELIAL-CELLS [J].
FRYER, RH ;
WILSON, BD ;
GUBLER, DB ;
FITZGERALD, LA ;
RODGERS, GM .
ARTERIOSCLEROSIS AND THROMBOSIS, 1993, 13 (09) :1327-1333
[5]   PROTEIN-SYNTHESIS ELONGATION-FACTOR EF-1-ALPHA IS ESSENTIAL FOR UBIQUITIN-DEPENDENT DEGRADATION OF CERTAIN N-ALPHA-ACETYLATED PROTEINS AND MAY BE SUBSTITUTED FOR BY THE BACTERIAL ELONGATION-FACTOR EF-TU [J].
GONEN, H ;
SMITH, CE ;
SIEGEL, NR ;
KAHANA, C ;
MERRICK, WC ;
CHAKRABURTTY, K ;
SCHWARTZ, AL ;
CIECHANOVER, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (16) :7648-7652
[6]   Tissue plasminogen activator binding to the annexin II tail domain - Direct modulation by homocysteine [J].
Hajjar, KA ;
Mauri, L ;
Jacovina, AT ;
Zhong, FM ;
Mirza, UA ;
Padovan, JC ;
Chait, BT .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (16) :9987-9993
[7]  
HAJJAR KA, 1990, J BIOL CHEM, V265, P2908
[8]   HOMOCYSTEINE-INDUCED MODULATION OF TISSUE-PLASMINOGEN ACTIVATOR BINDING TO ITS ENDOTHELIAL-CELL MEMBRANE-RECEPTOR [J].
HAJJAR, KA .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (06) :2873-2879
[9]  
HAJJAR KA, 1991, J BIOL CHEM, V266, P21962
[10]  
HAJJAR KA, 1994, J BIOL CHEM, V269, P21191