NR4A1 Aggravates Myocardial Ischaemia-Reperfusion Injury by Inhibiting OPA1-Mediated Mitochondrial Fusion.
J Cardiovasc Transl Res
; 16(5): 1050-1063, 2023 Oct.
Article
in En
| MEDLINE
| ID: mdl-37249897
ABSTRACT
Mitochondrial fusion is an important process that protects the myocardium. However, mitochondrial fusion is often inhibited in myocardial ischaemia-reperfusion injury (IR). The upstream mechanism of this effect is unclear. Nuclear receptor subfamily 4 group A member 1 (NR4A1) can aggravate myocardial IR and increase the level of oxidative stress, thereby affecting mitochondrial function and morphology. Inhibiting NR4A1 can improve oxidative stress levels and mitochondrial function and morphology, thereby reducing IR. Downregulating NR4A1 increases the expression level of the mitochondrial fusion-related protein optic atrophy 1 (OPA1), which is associated with these benefits. Inhibiting OPA1 expression with MYLS22 abrogates the effects of NR4A1 downregulation on IR. Furthermore, NR4A1 disrupts mitochondrial dynamics and activates the STING and NF-κB pathways. Insufficient mitochondrial fusion and increased apoptosis and inflammatory reactions worsen irreversible damage to cardiomyocytes. In conclusion, NR4A1 can exacerbate IR by inhibiting OPA1, causing mitochondrial damage.
Key words
Full text:
1
Collection:
01-internacional
Health context:
2_ODS3
/
6_ODS3_enfermedades_notrasmisibles
Database:
MEDLINE
Main subject:
Myocardial Reperfusion Injury
Limits:
Humans
Language:
En
Journal:
J Cardiovasc Transl Res
Year:
2023
Document type:
Article