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Titolo:
The GPIIIa (beta(3) integrin) P1(A) polymorphism in the early development of coronary atherosclerosis
Autore:
Mikkelsson, J; Perola, M; Penttila, A; Goldschmidt-Clermont, PJ; Karhunen, PJ;
Indirizzi:
Tampere Univ Hosp, Tampere 33014, Finland Tampere Univ Hosp Tampere Finland 33014 niv Hosp, Tampere 33014, Finland Natl Publ Hlth Inst, Dept Human Mol Genet, Helsinki, Finland Natl Publ Hlth Inst Helsinki Finland Human Mol Genet, Helsinki, Finland Univ Helsinki, Dept Forens Med, Helsinki, Finland Univ Helsinki HelsinkiFinland inki, Dept Forens Med, Helsinki, Finland Ohio State Univ, Heart & Lung Inst, Columbus, OH 43210 USA Ohio State Univ Columbus OH USA 43210 & Lung Inst, Columbus, OH 43210 USA Univ Kuopio, Dept Clin Pathol & Forens Med, FIN-70211 Kuopio, Finland UnivKuopio Kuopio Finland FIN-70211 rens Med, FIN-70211 Kuopio, Finland
Titolo Testata:
ATHEROSCLEROSIS
fascicolo: 3, volume: 154, anno: 2001,
pagine: 721 - 727
SICI:
0021-9150(20010215)154:3<721:TG(IPP>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
SMOOTH-MUSCLE CELLS; PLATELET GLYCOPROTEIN IIIA; PREMATURE MYOCARDIAL-INFARCTION; GENETIC RISK-FACTORS; TRANSFORMING GROWTH FACTOR-BETA(1); ARTERY DISEASE; PL(A2) POLYMORPHISM; INHERITED RISK; ALPHA(V)BETA(3) INTEGRIN; HEART-DISEASE;
Keywords:
platelet glycoprotein GPIIb-IIIa complex; blood platelets; integrins; atherosclerosis; polymorphism; genetics; coronary disease;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Mikkelsson, J Tampere Univ, Med Sch Bldg, Tampere 33014, Finland Tampere Univ Med Sch Bldg Tampere Finland 33014 14, Finland
Citazione:
J. Mikkelsson et al., "The GPIIIa (beta(3) integrin) P1(A) polymorphism in the early development of coronary atherosclerosis", ATHEROSCLER, 154(3), 2001, pp. 721-727

Abstract

The GPIIIa (beta (3) integrin) is an integral part of two glycoprotein receptors - the GP(IIb/IIIa) fibrinogen receptors in platelets and the GP(V/IIIa) vitronectin receptors in endothelium and vascular smooth muscle cells (VSMC). The pl(A) polymorphism of the gene for GPIIIa (beta (3) integrin) has been suggested to play an important role in the progression of coronary artery disease (CAD) and in coronary thrombosis. Whether the action of the Pl(A) polymorphism is due to differences in platelet aggregability or function of the VSMC and endothelial GPIIIa is not known. The association of the Pl(A) polymorphism with the early, non-complicated atherosclerosis and CAD was studied in the Helsinki Sudden Death Study (HSDS) comprising two independent, autopsy series of altogether 700 middle-aged Caucasian Finnish men (33-70 year) suffering sudden out-of-hospital death. The burden of complicated lesions was greater in men with the A2 allele (heterozygotes or homozygotes for A2) (P = 0.01) compared with Pl(A1/A1) homozygotes in the entire series. To further estimate the role of platelet-independent GPIIIa receptors, we excluded all cases with coronary thrombosis and thrombus-overlaid complicated lesions. In this subset of men, fibrous coronary lesions were more frequent (OR 2.9. P < 0.01) in the coronary arteries of Pl(A1/A1) homozygotes compared with men with the Pl(A2) allele. Moreover, men with the Pl(A1/A1) genotype also had more stenotic coronary arteries (P < 0.05) compared with men with the A2 allele at this early, non-complicated stage of atherosclerosis. The findings of this study suggest that Pl(A1/A1) homozygotes may be prone to early atherosclerosis and more rapid progression of stable CAD whereas carriers of the Pl(A2) allele are more prone to thrombotic complications. We hypothesize that the Pl(A) polymorphism may account for the early atherosclerosis by affecting the function of endothelial and vSMC GP(V/IIIa) receptors, whereas the Pl(A) polymorphism on platelet GP(IIb/IIIa) receptors may play a major role in coronary thrombosis. (C) 2001 Elsevier ScienceIreland Ltd. All rights reserved.

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Documento generato il 22/01/20 alle ore 12:16:52