Osteoprotegerin Disruption Attenuates HySu-Induced Pulmonary Hypertension Through Integrin αvß3/FAK/AKT Pathway Suppression.
Circ Cardiovasc Genet
; 10(1)2017 Feb.
Article
en En
| MEDLINE
| ID: mdl-28077433
ABSTRACT
BACKGROUND:
Pulmonary arterial remodeling characterized by increased vascular smooth muscle proliferation is commonly seen in life-threatening disease, pulmonary arterial hypertension (PAH). Clinical studies have suggested a correlation between osteoprotegerin serum levels and PAH severity. Here, we aimed to invhestigate vascular osteoprotegerin expression and its effects on pulmonary arterial smooth muscle cell proliferation in vitro and in vivo, as well as examine the signal transduction pathways mediating its activity. METHODS ANDRESULTS:
Serum osteoprotegerin levels were significantly elevated in patients with PAH and correlated with disease severity as determined by the World Health Organization (WHO) functional classifications and 6-minute walking distance tests. Similarly, increased osteoprotegerin expression was observed in the pulmonary arteries of hypoxia plus SU5416- and monocrotaline-induced PAH animal models. Moreover, osteoprotegerin disruption attenuated hypoxia plus SU5416-induced PAH progression by reducing pulmonary vascular remodeling, whereas lentiviral osteoprotegerin reconstitution exacerbated PAH by increasing pulmonary arterial smooth muscle cell proliferation. Furthermore, pathway analysis revealed that osteoprotegerin induced pulmonary arterial smooth muscle cell proliferation by interacting with integrin αvß3 to elicit downstream focal adhesion kinase and AKT pathway activation.CONCLUSIONS:
Osteoprotegerin facilitates PAH pathogenesis by regulating pulmonary arterial smooth muscle cell proliferation, suggesting that it may be a potential biomarker and therapeutic target in this disease.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_cobertura_universal
Asunto principal:
Pirroles
/
Transducción de Señal
/
Proteínas Proto-Oncogénicas c-akt
/
Quinasa 1 de Adhesión Focal
/
Osteoprotegerina
/
Presión Arterial
/
Hipertensión Pulmonar
/
Indoles
/
Hipoxia
/
Músculo Liso Vascular
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Circ Cardiovasc Genet
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
GENETICA MEDICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
China