C1q/TNF-related protein 1 prevents neointimal formation after arterial injury.
Atherosclerosis
; 257: 138-145, 2017 02.
Article
em En
| MEDLINE
| ID: mdl-28131048
ABSTRACT
BACKGROUND AND AIMS:
Obesity contributes to the progression of vascular disorders. C1q/TNF-related protein (CTRP) 1 is a circulating adipokine, which is upregulated in obese complications including coronary artery disease. Here, we investigated the role of CTRP1 in regulation of vascular remodeling after mechanical injury and evaluated its potential mechanism.METHODS:
Mice were subjected to wire-induced injury of left femoral arteries. An adenoviral vector encoding CTRP1 (Ad-CTRP1) or ß-galactosidase as a control was injected into the jugular vein of mice 3 days prior to surgery.RESULTS:
Systemic administration of Ad-CTRP1 to wild-type mice led to reduction of the neointimal thickening after wire-induced arterial injury and the number of bromodeoxyuridine-positive cells in injured vessels as compared with treatment with control vectors. Treatment of vascular smooth muscle cells (VSMCs) with CTRP1 protein attenuated proliferative activity and ERK phosphorylation in response to PDGF-BB. CTRP1 treatment increased cyclic AMP (cAMP) levels in VSMCs, and inhibition of adenylyl cyclase reversed the inhibitory effect of CTRP1 on VSMC growth and ERK phosphorylation. Antagonization of sphingosine-1-phosphaterote (S1P) receptor 2 blocked the effects of CTRP1 on cAMP production and VSMC growth. Furthermore, CTRP1-knockout mice had enhanced neointimal thickening following injury and increased numbers of proliferating cells in neointima compared to control WT mice.CONCLUSIONS:
These findings indicate that CTRP1 functions to prevent the development of pathological vascular remodeling by reducing VSMC growth through the cAMP-dependent pathway.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Miócitos de Músculo Liso
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Proliferação de Células
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Adipocinas
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Lesões do Sistema Vascular
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Neointima
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Músculo Liso Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article