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Titolo:
VIRUS-ENCODED SERINE PROTEINASE-INHIBITOR SERP-1 INHIBITS ATHEROSCLEROTIC PLAQUE DEVELOPMENT AFTER BALLOON ANGIOPLASTY
Autore:
LUCAS A; LIU LY; MACEN J; NASH P; DAI E; STEWART M; GRAHAM K; ETCHES W; BOSHKOV L; NATION PN; HUMEN D; HOBMAN ML; MCFADDEN G;
Indirizzi:
UNIV WESTERN ONTARIO,JOHN P ROBARTS RES INST,POB 5015,100 PERTH DR LONDON ON N6A 5K8 CANADA UNIV ALBERTA,DEPT MED,DIV CARDIOL EDMONTON AB CANADA UNIV ALBERTA,DEPT BIOCHEM EDMONTON AB CANADA UNIV ALBERTA,HLTH SCI LAB ANIM SERV EDMONTON AB CANADA UNIV ALBERTA,DEPT LAB MED & PATHOL EDMONTON AB CANADA
Titolo Testata:
Circulation
fascicolo: 11, volume: 94, anno: 1996,
pagine: 2890 - 2900
SICI:
0009-7322(1996)94:11<2890:VSPSIA>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
MUSCLE CELL-PROLIFERATION; MYXOMA VIRUS; PLASMINOGEN-ACTIVATOR; CORONARY RESTENOSIS; ARTERIAL INJURY; RABBIT; PATHOGENESIS; MODULATION; LEUKOCYTE; POXVIRUS;
Keywords:
PLAQUE; SERPIN; ANGIOPLASTY; IMMUNE SYSTEM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
A. Lucas et al., "VIRUS-ENCODED SERINE PROTEINASE-INHIBITOR SERP-1 INHIBITS ATHEROSCLEROTIC PLAQUE DEVELOPMENT AFTER BALLOON ANGIOPLASTY", Circulation, 94(11), 1996, pp. 2890-2900

Abstract

Background Recurrent atherosclerotic plaque growth, restenosis, is a significant clinical problem after interventional procedures. Initiation of restenosis involves activation of inflammatory and thrombotic cascades, which are regulated by serine proteinase enzymes and inhibitors. We have investigated the use of a viral serine proteinase inhibitor, SERP-1. to reduce plaque development after primary balloon angioplasty. This is the first experimental report of the use of a viral anti-inflammatory protein for the prevention of atherosclerosis. Methods andResults Seventy-four cholesterol-fed rabbits were treated with eitherlocal or systemic infusions of SERP-1 protein (or control solutions) after balloon-mediated injury. Sites of SERF-1 infusion in rabbits haddramatically reduced plaque compared with control infusions at the 4-week follow-up. At low-dose infusions (30 to 300 pg), only the primaryinfusion site had a demonstrable decrease in plaque, whereas at higher-dose infusions (>3000 pg), a generalized reduction in plaque development was detected. An associated decrease in mononuclear cell infiltration of the arterial wail was detected after SERF-1 infusion within the first 24 hours. Infusion of an active-site mutant of SERP-1 (P-1-P-1', ala-ala) lacking serine proteinase inhibitory activity failed to prevent plaque growth. Conclusions Purified SERP-1, a virus-encoded secreted glycoprotein, reduces plaque growth after primary balloon-mediated injury. Plaque development is decreased by inhibition of serine proteinase activity and is associated with a focal reduction in macrophageinfiltration immediately after injury. Investigation of serine proteinase inhibitors may provide new insight into the regulation of arterial responses to injury.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 10:12:59