Phoenixin 20 ameliorates pulmonary arterial hypertension via inhibiting inflammation and oxidative stress.
Aging (Albany NY)
; 16(6): 5027-5037, 2024 03 19.
Article
em En
| MEDLINE
| ID: mdl-38517365
ABSTRACT
Pulmonary arterial hypertension (PAH) is a severe pathophysiological syndrome resulting in heart failure, which is found to be induced by pulmonary vascular remodeling mediated by oxidative stress (OS) and inflammation. Phoenixin-20 (PNX-20) is a reproductive peptide first discovered in mice with potential suppressive properties against OS and inflammatory response. Our study will explore the possible therapeutic functions of PHN-20 against PAH for future clinical application. Rats were treated with normal saline, PHN-20 (100 ng/g body weight daily), hypoxia, hypoxia+PHN-20 (100 ng/g body weight daily), respectively. A signally elevated RVSP, mPAP, RV/LV + S, and W%, increased secretion of cytokines, enhanced malondialdehyde (MDA) level, repressed superoxide dismutase (SOD) activity, and activated NLRP3 signaling were observed in hypoxia-stimulated rats, which were notably reversed by PHN-20 administration. Pulmonary microvascular endothelial cells (PMECs) were treated with hypoxia with or without PHN-20 (10 and 20 nM). Marked elevation of inflammatory cytokine secretion, increased MDA level, repressed SOD activity, and activated NLRP3 signaling were observed in hypoxia-stimulated PMECs, accompanied by a downregulation of SIRT1. Furthermore, the repressive effect of PHN-20 on the domains-containing protein 3 (NLRP3) pathway in hypoxia-stimulated PMECs was abrogated by sirtuin1 (SIRT1) knockdown. Collectively, PHN-20 alleviated PAH via inhibiting OS and inflammation by mediating the transcriptional function of SIRT1.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hormônios Peptídicos
/
Hipertensão Arterial Pulmonar
/
Hipertensão Pulmonar
Limite:
Animals
Idioma:
En
Revista:
Aging (Albany NY)
Ano de publicação:
2024
Tipo de documento:
Article