Increased expression of the transforming growth factor-beta signaling pathway, endoglin, and early growth response-1 in stable plaques.
Stroke
; 40(2): 439-47, 2009 Feb.
Article
em En
| MEDLINE
| ID: mdl-19074480
ABSTRACT
BACKGROUND AND PURPOSE:
Unstable atherosclerotic plaques are characterized by increased macrophages and reduced smooth muscle cells (SMCs) and collagen content. Endoglin, an accessory transforming growth factor-beta (TGFbeta) receptor, is a modulator of TGFbeta signaling recently found to be expressed on SMCs in atherosclerotic plaques. Its function in plaque SMCs and plaque development is unknown. Early growth response-1 (EGR-1), a transcription factor downstream of TGFbeta, stimulates SMC proliferation and collagen synthesis. In atherosclerotic lesions, it is mainly expressed by SMCs. Therefore, we studied the TGFbeta, endoglin, and EGR-1 pathway in advanced atherosclerotic plaques in relation to plaque phenotype.METHODS:
Human carotid atherosclerotic plaques (n=103) were collected from patients undergoing carotid endarterectomy. Histologically, plaques were analyzed for plaque characteristics, ie, collagen, macrophage and SMC content, and intraplaque thrombus. Intraplaque endoglin, pSmad (indicative for TGFbeta signaling), EGR-1, and TGFbeta levels were analyzed using Western blots and enzyme-linked immunosorbent assays, respectively.RESULTS:
Higher endoglin and EGR-1 protein levels correlated positively with increased plaque collagen levels, increased smooth muscle cell content, and decreased intraplaque thrombi as well as TGFbeta signaling (pSmad). Although EGR-1 overexpression in vitro stimulated collagen synthesis, inhibiting endoglin resulted in lower EGR-1 levels, decreased SMC proliferation, and decreased collagen content.CONCLUSIONS:
TGFbeta in human atherosclerotic plaques is active and signals through the TGFbeta/Smad pathway. For the first time, we show a strong association between endoglin and EGR-1, increased collagen and SMCs expression, decreased levels of intraplaque thrombosis, and a stable plaque phenotype.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Antígenos CD
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Arteriosclerose Intracraniana
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Fator de Crescimento Transformador beta
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Receptores de Superfície Celular
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Proteína 1 de Resposta de Crescimento Precoce
Limite:
Aged
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Female
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Humans
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Male
Idioma:
En
Revista:
Stroke
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Holanda