Exosomes facilitate intercellular communication between uterine perivascular adipose tissue and vascular smooth muscle cells in pregnant rats

Abstract

Perivascular adipose tissue (PVAT) is distinct from other adipose depots as it has differential gene and protein profiles and vasoactive functions. We have shown that pregnancy affects the morphology of PVAT surrounding the uterine arteries (utPVAT) differentially than the morphology of non-perivascular reproductive adipose depots (i.e., periovarian adipose tissue, OVAT). Here, we hypothesized that pregnancy modifies the profile (size and molecular weight) of exosome-like extracellular vesicles released by utPVAT (Exo-utPVAT) compared to OVAT (Exo-OVAT) and that primary uterine vascular smooth muscle cells (utVSMCs) can internalize Exo-utPVAT. Our findings indicate that utPVAT from pregnant and non-pregnant rats secrete exosome-like vesicles. Exo-utPVAT from pregnant rats were smaller (i.e., molecular size) and heavier (i.e., molecular weight) than those from non-pregnant rats, while pregnancy did not affect the size of Exo-OVAT. Immunocytochemistry and confocal microscopy showed that primary utVSMCs internalized Exo-utPVAT (both tissues from the same pregnant rat) labeled by the lipophilic tracer DiO. Treatment of isolated uterine arteries with Exo-utPVAT did not affect relaxation responses to acetylcholine (ACh) in pregnant or non-pregnant rats. Collectively, these findings demonstrate a novel type of intercellular communication between Exo-utPVAT and utVSMCs and indicate pregnancy modulates the morphology and cargo of Exo-utPVAT.

Oxidative stress induces release of mitochondrial DNA into the extracellular space in human placental villous trophoblast BeWo cells

“…FBS was depleted of exosomes via ultracentrifugation (Thermo Scientific, Sorvall WX + Ultra Series) at 10,000 xg for 2 hours as previously described(21). The exosome-depleted FBS aqueous layer was then filtered through a 0.2 μm-sized 50-mL tube top vacuum filter system (cat# 430320, Corning, NY).…”

Perivascular Adipose Tissue and Uterine Artery Adaptations to Pregnancy

“…Interestingly, uterine PVAT secretes exosome-like extracellular vesicles that are taken up by adjacent vascular smooth muscle cells [155]. Uterine PVAT-derived exosomes increase in size with pregnancy and carry proteins of greater molecular weight compared to uterine PVAT-derived exosomes from nonpregnant rats [155]. The exact mechanisms underlying the trafficking of uterine PVAT-derived exosomes to vascular smooth muscle cells and its effects on the function of the maternal uterine artery wall are currently unknown.…”

“…Although the exact mechanisms by which uterine PVAT attains these vasoactive effects remain unknown, we demonstrated that uterine PVAT potentiates the release of thromboxane B 2 from uterine arteries, although inhibition of thromboxane receptor did not abolish the antidilatory effects of uterine PVAT on isolated uterine arteries [154]. Interestingly, uterine PVAT secretes exosome‐like extracellular vesicles that are taken up by adjacent vascular smooth muscle cells [155]. Uterine PVAT‐derived exosomes increase in size with pregnancy and carry proteins of greater molecular weight compared to uterine PVAT‐derived exosomes from nonpregnant rats [155].…”

Extracellular Vesicles in Adipose Tissue Communication with the Healthy and Pathological Heart

“…Interestingly, these modifications were restricted to uterine PVAT, while the periovarian adipose-tissue-derived EV profile was unchanged. These alterations modified EV morphology and cargo, with smaller vesicles of higher density in pregnant female rats, although the functional consequences for VSMC and vasorelaxation remain to be explored [65].…”