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

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.

Dilemma of Epigenetic Changes Causing or Reducing Metabolic Disorders in Offsprings of Obese Mothers

“…It was found that 12-month-old offspring of obese dams had increased body weight and fat mass and exhibited an elevated level of hepatic miR-582-3p and miR-582-5p [93]. Zhou et al characterised the exosomes from the adipose tissue of an obese sow and found they regulate endothelial cell migration and angiogenesis through miR-221 implicated in placental dysplasia during gestation [94]. A study analysed peroxisome proliferator-activated receptor (PPAR)-γ expression in cells of offspring from obese and overweight mothers and uncovered its relation with miRNAs [95].…”

Alterations in maternal plasma exosomal miRNAs revealed selective material exchange between maternal circulation and placenta

“…EVs derived from the human placenta could participate in regulating the maternal immune system and vascular network for successful pregnancy outcome 10–12 . The role of exosomes in placental vascular complications and pregnancy disorders also has been reported 13–16 . Our previous research indicated that exosomal miRNAs are important for regulating angiogenesis to maintain a normal pregnancy 17 .…”

“…[10][11][12] The role of exosomes in placental vascular complications and pregnancy disorders also has been reported. [13][14][15][16] Our previous research indicated that exosomal miRNAs are important for regulating angiogenesis to maintain a normal pregnancy. 17 We also found exosomes derived from women with preeclampsia could induce vascular dysfunction.…”

Circulating microvesicles miR139‐3p from bronchopulmonary dysplasia aggravates pulmonary vascular simplification by targeting 4E binding protein 1

“…Microvesicles carry various biological molecules, such as microRNAs (miRNAs), proteins and DNAs, which regulate the biological function of target cells 16 . Studies have reported that circulating vesicles inhibit endothelial cell angiogenesis through miR221‐mediated repression of Angpl2 17 . Eukaryotic translation initiation factor 4E binding protein 1 (4EBP1) is a translation inhibition protein family member.…”

“…16 Studies have reported that circulating vesicles inhibit endothelial cell angiogenesis through miR221-mediated repression of Angpl2. 17 Eukaryotic translation initiation factor 4E binding protein 1 (4EBP1) is a translation inhibition protein family member. However, 4EBP1 could also promote the translation process of VEGF, 18,19 HIF1α and BCL-2 20 under hypoxia conditions.…”