Specialized Proresolving Mediators Protect Against Experimental Autoimmune Myocarditis by Modulating Ca2+ Handling and NRF2 Activation.
JACC Basic Transl Sci
; 7(6): 544-560, 2022 Jun.
Article
in En
| MEDLINE
| ID: mdl-35818504
ABSTRACT
Specialized proresolving mediators and, in particular, 5(S), (6)R, 7-trihydroxyheptanoic acid methyl ester (BML-111) emerge as new therapeutic tools to prevent cardiac dysfunction and deleterious cardiac damage associated with myocarditis progression. The cardioprotective role of BML-111 is mainly caused by the prevention of increased oxidative stress and nuclear factor erythroid-derived 2-like 2 (NRF2) down-regulation induced by myocarditis. At the molecular level, BML-111 activates NRF2 signaling, which prevents sarcoplasmic reticulum-adenosine triphosphatase 2A down-regulation and Ca2+ mishandling, and attenuates the cardiac dysfunction and tissue damage induced by myocarditis.
8OHdG, 8-hydroxy-2'-deoxyguanosine; BML-111, 5(S), (6)R, 7-trihydroxyheptanoic acid methyl ester; Ctrl, control; Cys, cysteine; EAM, experimental autoimmune myocarditis; EC, excitation-contraction; Epi, 15-epi-lipoxin A4; LXA4, lipoxin A4; Lut, luteolin; NRF2; NRF2, nuclear factor erythroid-derived 2-like 2; SCR, spontaneous diastolic Ca2+ release; SERCA2A; SERCA2A, sarcoplasmic reticulumadenosine triphosphatase 2A; SPM, specialized proresolving mediator; SR, sarcoplasmic reticulum; Veh, vehicle; calcium handling; mRNA, messenger RNA; myocarditis; pro-resolving mediators
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
JACC Basic Transl Sci
Year:
2022
Document type:
Article
Affiliation country:
Spain