Circulating Exosomal miR-221 from Maternal Obesity Inhibits Angiogenesis via Targeting Angptl2

Maternal obesity disrupts both placental angiogenesis and fetus development. However, the links between adipocytes and endothelial cells in maternal obesity are not fully understood. The aim of this study was to characterize exosome-enriched miRNA from obese sow's adipose tissue and evaluate the effect on angiogenesis of endothelial cells. Plasma exosomes were isolated and analyzed by nanoparticle tracking analysis (NTA), electron morphological analysis, and protein marker expression. The number of exosomes was increased as the gestation of the sows progressed. In addition, we found that exosomes derived from obese sows inhibited endothelial cell migration and angiogenesis. miRNA detection showed that miR-221, one of the miRNAs, was significantly enriched in exosomes from obese sows. Further study demonstrated that exosomal miR-221 inhibited the proliferation and angiogenesis of endothelial cells through repressing the expression of Angptl2 by targeting its 3 & PRIME; untranslated region. In summary, miR-221 was a key component of the adipocyte-secreted exosomal vesicles that mediate angiogenesis. Our study may be a novel mechanism showing the secretion of harmful exosomes from obesity adipose tissues causes placental dysplasia during gestation.

Automated summary

The study revealed that exosomes from obese sows, particularly enriched with miR-221, inhibit endothelial cell migration and angiogenesis by suppressing the expression of Angptl2. This suggests that miR-221 plays a key role in mediating angiogenesis through adipocyte-secreted exosomal vesicles. The findings indicate a novel mechanism where harmful exosomes secreted from obesity adipose tissues lead to placental dysplasia during gestation.