Rutaecarpine prevents hypertensive cardiac hypertrophy involving the inhibition of Nox4-ROS-ADAM17 pathway.
J Cell Mol Med
; 23(6): 4196-4207, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30953402
ABSTRACT
Rutaecarpine attenuates hypertensive cardiac hypertrophy in the rats with abdominal artery constriction (AAC); however, its mechanism of action remains largely unknown. Our previous study indicated that NADPH oxidase 4 (Nox4) promotes angiotensin II (Ang II)-induced cardiac hypertrophy through the pathway between reactive oxygen species (ROS) and a disintegrin and metalloproteinase-17 (ADAM17) in primary cardiomyocytes. This research aimed to determine whether the Nox4-ROS-ADAM17 pathway is involved in the protective action of rutaecarpine against hypertensive cardiac hypertrophy. AAC-induced hypertensive rats were adopted to evaluate the role of rutaecarpine in hypertensive cardiac hypertrophy. Western blotting and real-time PCR were used to detect gene expression. Rutaecarpine inhibited hypertensive cardiac hypertrophy in AAC-induced hypertensive rats. These findings were confirmed by the results of in vitro experiments that rutaecarpine significantly inhibited Ang II-induced cardiac hypertrophy in primary cardiomyocytes. Likewise, rutaecarpine significantly suppressed the Nox4-ROS-ADAM17 pathway and over-activation of extracellular signal-regulated kinase (ERK) 1/2 pathway in the left ventricle of AAC-induced hypertensive rats and primary cardiomyocytes stimulated with Ang II. The inhibition of Nox4-ROS-ADAM17 pathway and over-activation of ERK1/2 might be associated with the beneficial role of rutaecarpine in hypertensive cardiac hypertrophy, thus providing additional evidence for preventing hypertensive cardiac hypertrophy with rutaecarpine.
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Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
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Cardiomegalia
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Alcaloides Indólicos
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Proteína ADAM17
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NADPH Oxidase 4
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Hipertensão
Tipo de estudo:
Etiology_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article