Small extracellular vesicles (EVs) have become essential mediators of intercellular and inter-organ communication in vivo, with significant therapeutic potential and prognostic value in cardiovascular diseases. Despite extensive research on exosomal cargoes and their biological effects, the in vivo dynamics and systemic distribution of cardiac-derived small EVs under pathological conditions remain poorly understood. This study used cardiac exosome-tracking mice to profile the distribution and production of cardiomyocyte-derived small EVs following myocardial infarction (MI). We observed distinct temporal dynamics in cardiac exosome uptake between males and females. In the heart, uptake increased markedly during the acute injury phase and declined during the healing phase in males, while it gradually declined in females, with both sexes showing preferential uptake by endothelial cells and leukocytes. The distribution of cardiac-derived small EVs in peripheral organs gradually decreased over time in male mice but followed different patterns in females. Females exhibited higher circulating levels of cardiac-derived small EVs and a more dynamic uptake into peripheral organs than males. Meanwhile, cardiac exosome biogenesis tended to increase on day 3 but significantly decreased by day 14 in male MI hearts, while it increased in females as MI progressed. These findings provide the first comprehensive in vivo spatial and temporal map of endogenous cardiac exosome dynamics after MI and its sexual dimorphism, laying a crucial foundation for future mechanistic studies.
Chen et al. (Mon,) studied this question.