Asprosin contributes to vascular remodeling in hypertensive rats via superoxide signaling.
J Hypertens
; 42(8): 1427-1439, 2024 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-38690935
ABSTRACT
OBJECTIVE:
Proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to vascular remodeling. Asprosin, a newly discovered protein hormone, is involved in metabolic diseases. Little is known about the roles of asprosin in cardiovascular diseases. This study focused on the role and mechanism of asprosin on VSMC proliferation and migration, and vascular remodeling in a rat model of hypertension. METHODS ANDRESULTS:
VSMCs were obtained from the aortic media of 8-week-old male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Asprosin was upregulated in the VSMCs of SHR. For in vitro studies, asprosin promoted VSMC proliferation and migration of WKY and SHR, and increased Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity, NOX1/2/4 protein expressions and superoxide production. Knockdown of asprosin inhibited the proliferation, migration, NOX activity, NOX1/2 expressions and superoxide production in the VSMCs of SHR. The roles of asprosin in promoting VSMC proliferation and migration were not affected by hydrogen peroxide scavenger, but attenuated by superoxide scavenger, selective NOX1 or NOX2 inhibitor. Toll-like receptor 4 (TLR4) was upregulated in SHR, TLR4 knockdown inhibited asprosin overexpression-induced proliferation, migration and oxidative stress in VSMCs of WKY and SHR. Asprosin was upregulated in arteries of SHR, and knockdown of asprosin in vivo not only attenuated oxidative stress and vascular remodeling in aorta and mesentery artery, but also caused a subsequent persistent antihypertensive effect in SHR.CONCLUSIONS:
Asprosin promotes VSMC proliferation and migration via NOX-mediated superoxide production. Inhibition of endogenous asprosin expression attenuates VSMC proliferation and migration, and vascular remodeling of SHR.
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Base de dados:
MEDLINE
Assunto principal:
Ratos Endogâmicos SHR
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Ratos Endogâmicos WKY
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Transdução de Sinais
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Movimento Celular
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Superóxidos
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Proliferação de Células
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Remodelação Vascular
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Hipertensão
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Músculo Liso Vascular
Limite:
Animals
Idioma:
En
Revista:
J Hypertens
Ano de publicação:
2024
Tipo de documento:
Article