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Titolo:
Gene targeting in hemostasis. Alpha(2)-antiplasmin
Autore:
Lijnen, HR;
Indirizzi:
Univ Louvain, Ctr Mol & Vasc Biol, B-3000 Louvain, Belgium Univ Louvain Louvain Belgium B-3000 & Vasc Biol, B-3000 Louvain, Belgium
Titolo Testata:
FRONTIERS IN BIOSCIENCE
, volume: 6, anno: 2001,
pagine: D239 - D247
SICI:
1093-9946(20010201)6:<D239:GTIHA>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMINO-ACID-SEQUENCE; ALPHA-2-PLASMIN INHIBITOR; HUMAN ALPHA-2-ANTIPLASMIN; FIBRINOLYTIC SYSTEM; PHYSIOLOGICAL FIBRINOLYSIS; HUMAN ANTIPLASMIN; HUMAN-PLASMA; SITE; DEFICIENCY; PLASMINOGEN;
Keywords:
fibrinolysis; plasmin; alpha(2)-antiplasmin; gene inactivation; thrombosis; bleeding; alpha(2)-antiplasmin deficiency; review;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Lijnen, HR Univ Louvain, Ctr Mol & Vasc Biol, Campus Gasthuisberg,O&N,Herestr 49, B-3000 Louvain, Belgium Univ Louvain Campus Gasthuisberg,O&N,Herestr 49 Louvain Belgium B-3000
Citazione:
H.R. Lijnen, "Gene targeting in hemostasis. Alpha(2)-antiplasmin", FRONT BIOSC, 6, 2001, pp. D239-D247

Abstract

Apha(2)-antiplasmin (AP), the main physiological plasmin inhibitor in mammalian plasma, is a 70 kDa single chain serpin (serine proteinase inhibitor)with reactive site peptide bond Arg-Met. It inhibits plasmin very rapidly (second-order inhibition rate constant of 2 x 10(7) M-1.s(-1)) following formation of an inactive 1:1 stoichiometric complex. The high reaction rate requires the presence of a free active site and free lysine-binding site(s) in plasmin. The pathophysiologic relevance of AP is suggested by the finding that homozygous deficient patients show a bleeding tendency; heterozygotes, in contrast, frequently have no or only mild bleeding complications. Inactivation of the AP gene in mice was achieved by replacing, via homologous recombination in embryonic stem cells, a 7 kb genomic sequence encoding theentire murine protein with the neomycin resistance expression cassette. Homozygous AP deficient mice display normal fertility, viability and development. They have an enhanced endogenous fibrinolytic capacity without overt bleeding; this is reflected by a higher spontaneous lysis rate of experimental pulmonary emboli, by a reduced fibrin deposition in the kidneys following challenge with endotoxin, by more limited photochemically induced arterial thrombosis, and by reduced infarct size following induction of focal cerebral ischemia by ligation of the left middle cerebral artery. In a vascularinjury restenosis model, AP deficiency has no significant effect on smoothmuscle cell migration and neointima formation. These data suggest that, atleast in the murine system, the main role of alpha(2)-antiplasmin is in regulating plasmin activity in the circulating blood and in controlling intravascular fibrinolysis.

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Documento generato il 25/01/20 alle ore 06:24:52