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

Yuanfei Zhou,Chenbin Cui,Hongkui Wei,Siwen Jiang,Mao Xia,Jian Peng

doi:10.3390/ijms221910343

Abstract

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′ 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.

Highlights

Accepted: 21 September 2021In modern society, obesity has become a serious hazard to human health
Nanoparticle tracking analysis showed that particles ranged from to nm in diameter, with an average of 87 ± 30 nm (Figure 1A)
In miR-10b and miR-17, there was no significant difference in proliferation, and angiogenesis of endothelial cells (Figure S1). These results show that exosomal miR-221 could repress the proliferation and angiogenesis of endothelial cells

Summary

Introduction

Obesity has become a serious hazard to human health Maternal obesity impacts both the placenta and the fetus, often resulting in fetal overgrowth and a greater frequency of large for gestational age (LGA) infants [1]. Studies have shown that maternal obesity promotes a lipotoxic placental environment and inhibits placental angiogenesis in humans [7], as well as in some animals, such as ewes [8] and sows [3]. This in turn causes placental morphology, blood flow, fetomaternal exchanges, and endocrine function [9]

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