Urolithin A Protects against Hypoxia-Induced Pulmonary Hypertension by Inhibiting Pulmonary Arterial Smooth Muscle Cell Pyroptosis via AMPK/NF-κB/NLRP3 Signaling.
Int J Mol Sci
; 25(15)2024 Jul 28.
Article
in En
| MEDLINE
| ID: mdl-39125817
ABSTRACT
Recent studies confirmed that pyroptosis is involved in the progression of pulmonary hypertension (PH), which could promote pulmonary artery remodeling. Urolithin A (UA), an intestinal flora metabolite of ellagitannins (ETs) and ellagic acid (EA), has been proven to possess inhibitory effects on pyroptosis under various pathological conditions. However, its role on PH remained undetermined. To investigate the potential of UA in mitigating PH, mice were exposed to hypoxia (10% oxygen, 4 weeks) to induce PH, with or without UA treatment. Moreover, in vitro experiments were carried out to further uncover the underlying mechanisms. The in vivo treatment of UA suppressed the progression of PH via alleviating pulmonary remodeling. Pyroptosis-related genes were markedly upregulated in mice models of PH and reversed after the administration of UA. In accordance with that, UA treatment significantly inhibited hypoxia-induced pulmonary arterial smooth muscle cell (PASMC) pyroptosis via the AMPK/NF-κB/NLRP3 pathway. Our results revealed that UA treatment effectively mitigated PH progression through inhibiting PASMC pyroptosis, which represents an innovative therapeutic approach for PH.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pulmonary Artery
/
Signal Transduction
/
NF-kappa B
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Coumarins
/
Myocytes, Smooth Muscle
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AMP-Activated Protein Kinases
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Pyroptosis
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NLR Family, Pyrin Domain-Containing 3 Protein
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Hypertension, Pulmonary
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Hypoxia
Limits:
Animals
Language:
En
Journal:
Int J Mol Sci
Year:
2024
Document type:
Article
Affiliation country:
China