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Titolo:
Inhibition of transplant vasculopathy in a rat aortic allograft model after infusion of anti-inflammatory viral serpin
Autore:
Miller, LW; Dai, E; Nash, P; Liu, LY; Icton, C; Klironomos, D; Fan, L; Nation, PN; Zhong, R; McFadden, G; Lucas, A;
Indirizzi:
Univ Western Ontario, John P Robarts Res Inst, Vasc Biol Res Grp, London, ON N6A 5K8, Canada Univ Western Ontario London ON Canada N6A 5K8 London, ON N6A 5K8, Canada Univ Minnesota, Div Cardiovasc, Minneapolis, MN 55455 USA Univ Minnesota Minneapolis MN USA 55455 iovasc, Minneapolis, MN 55455 USA Univ Alberta, Cardiovasc Dis Res Grp, Dept Biochem, Edmonton, AB, Canada Univ Alberta Edmonton AB Canada Grp, Dept Biochem, Edmonton, AB, Canada Univ Alberta, Dept Lab Anim Med, Edmonton, AB, Canada Univ Alberta Edmonton AB Canada Dept Lab Anim Med, Edmonton, AB, Canada Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6A 5K8, CanadaUniv Western Ontario London ON Canada N6A 5K8 London, ON N6A 5K8, Canada Univ Western Ontario, Dept Surg, London, ON N6A 5K8, Canada Univ Western Ontario London ON Canada N6A 5K8 London, ON N6A 5K8, Canada
Titolo Testata:
CIRCULATION
fascicolo: 13, volume: 101, anno: 2000,
pagine: 1598 - 1605
SICI:
0009-7322(20000404)101:13<1598:IOTVIA>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
CORONARY-ARTERY DISEASE; SERINE PROTEINASE-INHIBITOR; CARDIAC TRANSPLANTATION; IMMUNOSUPPRESSIVE THERAPY; HEART-TRANSPLANTATION; CHRONIC REJECTION; VASCULAR-DISEASE; RISK-FACTORS; IN-VIVO; EXPRESSION;
Keywords:
rejection; transplantation; viruses; serpin; inflammation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Lucas, A Univ Western Ontario, John P Robarts Res Inst, Vasc Biol Res Grp,100 Perth Dr,POB 5015, London, ON N6A 5K8, Canada Univ Western Ontario 100Perth Dr,POB 5015 London ON Canada N6A 5K8
Citazione:
L.W. Miller et al., "Inhibition of transplant vasculopathy in a rat aortic allograft model after infusion of anti-inflammatory viral serpin", CIRCULATION, 101(13), 2000, pp. 1598-1605

Abstract

Background-Transplant vasculopathy remains a difficult therapeutic problem, resulting in the majority of late cardiac graft losses. This chronic vascular disease is thought to be triggered by alloantigen-dependent and alloantigen-independent inflammatory factors. Despite improved I-year survival, the incidence of transplant vasculopathy has not improved with current immunosuppressive protocols. Highly effective strategies have evolved in the large DNA viruses that shield infecting viruses from host inflammatory responses. Serp-1 is a secreted myxoma virus anti-inflammatory serine proteinase inhibitor. Serp-1 inhibits plasminogen activators in a manner similar to plasminogen activator inhibitor (PAI-I), a vascular protein that plays a pivotal regulatory role in vascular wound healing. In this study, we tested the ability of purified Serp-1 protein to ameliorate posttransplant vasculopathy after rat aortic allograft surgery. Methods and Results-Serp-1 protein or controls were infused into 98 rats immediately after segmental aortic allograft transplantation. After either late (28 days, 64 rats) or early (12 to 48 hours, 24 rats) follow-up, transplanted aortic segments were harvested for morphological and immunohistochemical analysis. Significant reductions in intimal plaque growth (P<0.002) and mononuclear cell invasion (P<0.033) were detected after Serp-1 infusion at nanogram doses. Serp-1 reduced early macrophage (P<0.0016) and nonspecific lymphocyte (P<0.0179) invasion into medial and adventitial layers and inhibited associated depletion of medial smooth muscle cells (P<0.0006). Conclusions-Infusion of a viral anti-inflammatory serpin, Serp-1, significantly reduces early inflammatory responses and later luminal occlusion in arat aortic allograft model.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 20:41:29