Abstract Body: Background: Exosomes’ beneficial effects on the injured hearts show promising results. Understanding the biodistribution and kinetics of cardiac exosomes during myocardial infarction (MI) is crucial for exploring the underlying mechanisms.
Aim: We aimed to elucidate dynamic biodistributions of cardiomyocyte-released exosomes in MI hearts at post-MI day 3 and day 14, representing the acute and remodeling stages, respectively. We employed the cardiac exosome reporter mice expressing CD63NanoLuc to track the endogenous cardiac exosomes.
Method: The NanoLuc reporter mice underwent MI surgery (n=3-12/group). Reporter expression was induced by tamoxifen injection. To assess post-MI cardiac exosome distribution via circulation, fourteen organs, and plasma exosomes were harvested for luciferase activity quantification at each time point. Bioluminescence analysis was conducted in isolated cardiac fibroblasts, endothelial cells, and leukocytes to profile exosome-mediated paracrine signaling.
Result: Plasma exosome luciferase activities were consistent across groups. A decline in bioluminescent levels was observed in all organs at both time points, with significant differences in the pancreas, thyroid, kidney, lung, and thymus (p<0.05). Day 3 post-MI showed increased heart endothelial cell bioluminescence in risk and remote areas (p=0.0007), whereas day 14 showed decreased bioluminescence in cardiac fibroblasts in both areas (p=0.0029 and p=0.0086). Endothelial cells and leukocytes exhibited a ten-fold higher exosome uptake than cardiac fibroblasts.
Conclusion: There was a significant decrease in exosome uptake by major organs from the injured heart. Cardiac endothelial cells and fibroblasts demonstrated dynamic exosome uptake changes, with endothelial cells and leukocytes showing notably higher uptake compared to fibroblasts.