The inventors showed that intravenous administration of the small
extracellular vesicles (sEVs) loaded with a
plasmid encoding a dominant-negative
mutant of NLRP3 under the control of the SF1
promoter (SF1-NLRP3-DN) slightly reduced
body weight but did not modify
food intake in atherosclerosis-prone ApoE knockout mice fed a high-
fat diet, but induced an increase in brow
adipose tissue (BAT)
thermogenesis. Glucose tolerance was not affected
after treatment with SF1-NLRP3-DN-loaded EVs. High-
fat diet feeding induced an increase in the number of arrhythmias, as well as an increase in the onset of
atrial fibrillation (AF) induced by transoesophageal stimulation, but also spontaneous arrhythmias that was not modified by the treatment with non-loaded EVs. Interestingly, EVs loaded with SF1-NLRP3-DN almost completely prevented both induced and spontaneous arrhythmias (conduction block) and AF. Finally, echocardiographic analyses showed that SF1-NLRP3-DN-loaded EVs did not induce any change in the structural and functional capacity of the heart. Accordingly, the present invention relates to the use of particles for the treatment of cardiac events associated with
obesity.