Aggregating human platelets stimulate the expression of thrombin receptors in cultured vascular smooth muscle cells via the release of transforming growth factor-beta1 and platelet-derived growth factorAB.
Circulation
; 96(11): 3888-96, 1997 Dec 02.
Article
em En
| MEDLINE
| ID: mdl-9403612
ABSTRACT
BACKGROUND:
Thrombin and the thrombin receptor have been implicated in the proliferation of vascular smooth muscle cells (VSMCs) observed after angioplasty and in atherosclerosis. Because thrombin receptor activation is an irreversible proteolytic event, the marked upregulation of the smooth muscle cell thrombin receptor after vascular injury may account for the maintained mitogenic activity of thrombin. The present study was designed to determine whether aggregating platelets stimulate thrombin receptor expression in cultured VSMCs and, if so, to identify the mediators. METHODS ANDRESULTS:
Thrombin receptor expression was assessed by Northern and Western blot analyses and functionally by measuring the release of 6-keto prostaglandin F1alpha. Platelet-derived products (PDPs) released by aggregating human platelets enhanced thrombin receptor mRNA levels in a time- and concentration-dependent manner, an effect that was potentiated by transient acidification of PDPs, which release bioactive transforming growth factor (TGF)-beta1, and that was slightly inhibited by ketanserin. Among several factors known to be released by aggregating platelets, only TGF-beta1, platelet-derived growth factorAB (PDGF(AB)), and serotonin mimicked the PDP effect. The level of membrane thrombin receptor protein was increased in TGF-beta1-treated VSMCs. Pretreatment of VSMCs with either acidified PDP, or TGF-beta1 increased the alpha-thrombin-stimulated release of 6-keto prostaglandin F1alpha. This effect was blunted by incubating acidified PDP with either a TGF-beta- or a PDGF-neutralizing antibody.CONCLUSIONS:
Aggregating human platelets stimulate the expression of thrombin receptors in VSMCs through the release of TGF-beta1, PDGF(AB), and, to a lesser extent, serotonin. The upregulation of the thrombin receptor by products released by aggregating platelets may sustain the mitogenic activity of thrombin in the vascular wall at sites of injury.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Derivado de Plaquetas
/
Agregação Plaquetária
/
Fator de Crescimento Transformador beta
/
Receptores de Trombina
/
Músculo Liso Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Circulation
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Alemanha