Specialized Proresolving Mediators Protect Against Experimental Autoimmune Myocarditis by Modulating Ca2+ Handling and NRF2 Activation

Resolution of Heart Failure Inflammation

“…In this issue of JACC: Basic to Translational Science , Val-Blasco et al 3 show that the ALX/FPR2 receptor agonist BML-111 reduced cardiac immune cell infiltration in a murine autoimmune myocarditis model. This is in line with previous work showing that ALX/FPR2 is up-regulated during acute myocardial ischemia and limits myocardial necrosis and neutrophil granulocyte infiltration after experimental coronary obstruction.…”

“… 1 By showing that ALX/FPR2 stimulation prevented myocarditis-induced left ventricular dysfunction, the observations in this issue introduce the notion of stimulating a resolution of inflammation by SPMs to improve cardiac function. 3 …”

“…Importantly, 15-epi-LXA 4 , which is a stable SPM ligand for ALX/FPR2, directly counteracted mishandling of intracellular Ca 2+ in isolated cardiomyocytes by stopping a down-regulation of the Ca 2+ channel SERCA2a through activation of NRF2. 3 …”

“…Val-Blasco et al 3 also present the translational implications by transcriptomic exploration of human cardiac samples. These results show the cardiac presence of the SPM biosynthesis enzymes and point to the ligand being crucial because the ALX/FPR2 receptor was not altered between healthy myocardium and cardiac tissue from individuals with myocarditis.…”

“…In their study, 3 stimulating the resolution of inflammation through SPM signaling emerges as a therapeutic tool to prevent cardiac dysfunction and deleterious cardiac damage associated with myocarditis. COVID-19 as a trigger of myocarditis is an important issue at present.…”