IQGAP1 promotes the phenotypic switch of vascular smooth muscle by myocardin pathway: a potential target for varicose vein.
Int J Clin Exp Pathol
; 7(10): 6475-85, 2014.
Article
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| MEDLINE
| ID: mdl-25400725
ABSTRACT
Recently, the architectural remodeling of venous vessel wall ranks as the basis of varicose veins development based on the phenotypic state of vascular smooth muscle cells (VSMCs). In this study, we firstly demonstrated an obvious up-regulation of IQ-domain GTPase-activating protein 1 (IQGAP1) in patients with varicose veins. Importantly, following stimulation with PDGF-BB for 4 h, a common inducer of phenotypic switch in VSMCs, a dramatically time-dependent increase in IQGAP1 expression was observed in human venous smooth muscle cells (HUVSMCs), concomitant with the down-regulation of SMC markers [including α-smooth muscle actin (SMA), smooth muscle calponin (CNN), SM22α (SM22)], suggesting a critical function of IQGAP1 during the switch of synthetic VSMC phenotype. Further analysis ascertained that IQGAP1 overexpression significantly inhibited the expression of SMA, SM and CNN, while its silencing dramatically promoted their expression levels. Moreover, the elevated IQGAP1 enhanced cell proliferation, migration and rearrangement. Mechanism assay confirmed that IQGAP1 overexpression notably blocked myocardin levels. Importantly, after transfection with myocardin siRNA, IQGAP1 down-regulation-induced decrease in cell proliferation, migration and cell rearrangement was remarkably attenuated. Together, these results demonstrated that IQGAP1 may regulate the phenotypic switch of VSMCs by myocardin pathway, which is critical for the pathological progression of varicose vein. Therefore, this study supports a prominent insight into how IQGAP1 possesses its benefit function in varicose veins development by regulating vascular remodeling.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Várices
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Proteínas Nucleares
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Transducción de Señal
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Transactivadores
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Proteínas Activadoras de ras GTPasa
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Miocitos del Músculo Liso
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Remodelación Vascular
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Músculo Liso Vascular
Tipo de estudio:
Observational_studies
Límite:
Adult
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Aged
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Humans
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Middle aged
Idioma:
En
Revista:
Int J Clin Exp Pathol
Asunto de la revista:
PATOLOGIA
Año:
2014
Tipo del documento:
Article