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The protective mechanism of sevoflurane in pulmonary arterial hypertension via downregulation of TRAF6.
Wang, Guan; Wang, Chun; Zhu, Pengcheng; Tian, Jiaxin; Yang, Haitao.
Afiliación
  • Wang G; Department of Anesthesiology, The Second Hospital of Dalian Medical University, Dalian 116023, Liaoning, China.
  • Wang C; Department of Anesthesiology, The Second Hospital of Dalian Medical University, Dalian 116023, Liaoning, China.
  • Zhu P; Department of Anesthesiology, The Second Hospital of Dalian Medical University, Dalian 116023, Liaoning, China.
  • Tian J; Department of Anesthesiology, The Second Hospital of Dalian Medical University, Dalian 116023, Liaoning, China. Electronic address: dltjx@163.com.
  • Yang H; Department of Anesthesiology, The Second Hospital of Dalian Medical University, Dalian 116023, Liaoning, China. Electronic address: haitaoyangdl@163.com.
Toxicol Appl Pharmacol ; 491: 117065, 2024 Oct.
Article en En | MEDLINE | ID: mdl-39127353
ABSTRACT
Pulmonary arterial hypertension (PAH) is an obstructive vasculopathy that, if not promptly treated, culminates in right heart failure. Therefore, pre-clinical studies are needed to support and optimize therapeutic approaches of PAH. Here, we explore a prospective function of sevoflurane in experimental PAH through regulating TRAF6. Monocrotaline (MCT)-induced PAH rats were subjected to sevoflurane inhalation and intratracheal instillation of lentivirus overexpressing TRAF6. Platelet-derived growth factor (PDGF)-treated pulmonary artery smooth muscle cells (PASMCs) were exposed to sevoflurane and genetically manipulated for TRAF6 overexpression. It was found that MCT and PDGF challenge upregulated the levels of TRAF6 in rat lung tissues and PASMCs, but sevoflurane treatment led to reduced TRAF6 expression. Sevoflurane inhalation in MCT-induced rats resulted in alleviative pulmonary vascular remodeling, mitigated right ventricular dysfunction and hypertrophy, improved mitochondrial function and dynamics, and inactivation of NF-κB pathway. In vitro studies confirmed that exposure to sevoflurane repressed PDGF-induced proliferation, migration, and phenotype switching of PASMCs, and suppressed mitochondrial dysfunction and NF-κB activation in PDGF-stimulated PASMCs. The beneficial impact of sevoflurane on pathological changes of lung and cell phenotype of PASMCs were reversed by overexpression of TRAF6. In summary, our study suggested the protective properties of sevoflurane in targeting PAH by downregulating TRAF6 expression, providing a novel avenue for the management of PAH.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Arteria Pulmonar / Regulación hacia Abajo / Ratas Sprague-Dawley / Miocitos del Músculo Liso / Factor 6 Asociado a Receptor de TNF / Sevoflurano / Hipertensión Arterial Pulmonar Límite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Arteria Pulmonar / Regulación hacia Abajo / Ratas Sprague-Dawley / Miocitos del Músculo Liso / Factor 6 Asociado a Receptor de TNF / Sevoflurano / Hipertensión Arterial Pulmonar Límite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China