Cyclooxygenase-dependent mechanisms mediate in part the anti-dilatory effects of perivascular adipose tissue in uterine arteries from pregnant rats

Osikoya, Oluwatobiloba; Cushen, Spencer C.; Ricci, Contessa A.; Goulopoulou, Styliani

doi:10.1016/j.phrs.2021.105788

Cited by 4 publications

(10 citation statements)

References 61 publications

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“…Male rats (15–26 wk of age) were used only for mating. Euthanasia and tissue harvest of all animals were performed on GD16 ( 5 , 6 ) between 8:00 AM and 10:00 AM. PVAT tissue cultures were immediately established after tissue harvest, and extracellular vesicles were isolated the next day.…”

Section: Methodsmentioning

confidence: 99%

“…Uterine artery remodeling in rodents occurs between gestational days 15–18 ( 18 , 19 ). Furthermore, our previous studies on the vasoactive effects of PVAT and the effects of pregnancy on PVAT protein/gene profile have been performed on GD16 ( 5 , 6 ). Thus, in the present study, all pregnant rats were tested on GD16 .…”

Section: Methodsmentioning

confidence: 99%

“…Exosome-free supernatants were used as negative controls. Purified exosomal samples were reconstituted in ice-cold T-PER Tissue Protein Extraction reagent, and the concentration of extracted proteins was determined with a modified bicinchoninic acid protein assay as in other studies ( 6 , 17 , 22 ). Proteins (30 µg) were resolved by electrophoresis on precast gradient 4%–20% SDS-PAGE gels (Cat.…”

Section: Methodsmentioning

confidence: 99%

“…We recently showed that perivascular adipose tissue surrounding uterine arteries (utPVAT) contributed to increases in uterine artery blood flow in pregnant but not in nonpregnant rats ( 5 ). In addition, utPVAT-conditioned media reduced relaxation responses to acetylcholine (ACh) in isolated uterine arteries ( 5 , 6 ). These effects were explained in part by pregnancy-induced changes in responsiveness of the uterine vascular wall to utPVAT-derived factors ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies reported that similar to nonperivascular adipose tissues ( 10 – 12 ), PVAT also secretes extracellular vesicles ( 13 – 15 ). Our previous studies have shown that pregnancy, which is a physiological state of dynamic changes and adaptations, affects PVAT morphology, genotypic profile, and vasodilatory properties ( 5 , 6 ). Interestingly, pregnancy differentially affected utPVAT morphology compared with periovarian adipose tissue (OVAT), which is a nonperivascular adipose tissue surrounding reproductive organs and thus in proximity with utPVAT.…”

Section: Introductionmentioning

confidence: 99%

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

Osikoya

Cushen

Gardner

et al. 2022

American Journal of Physiology-Heart and Circulatory Physiology

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Osikoya

Cushen

Gardner

et al. 2022

American Journal of Physiology-Heart and Circulatory Physiology

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Perivascular Adipose Tissue and Uterine Artery Adaptations to Pregnancy

Osikoya,

Hula,

da Silva

et al. 2024

Microcirculation

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Pregnancy is characterized by longitudinal maternal, physiological adaptations to support the development of a fetus. One of the cardinal maternal adaptations during a healthy pregnancy is a progressive increase in uterine artery blood flow. This facilitates sufficient blood supply for the development of the placenta and the growing fetus. Regional hemodynamic changes in the uterine circulation, such as a vast reduction in uterine artery resistance, are mainly facilitated by changes in uterine artery reactivity and myogenic tone along with remodeling of the uterine arteries. These regional changes in vascular reactivity have been attributed to pregnancy‐induced adaptations of cell‐to‐cell communication mechanisms, with an emphasis on the interaction between endothelial and vascular smooth muscle cells. Perivascular adipose tissue (PVAT) is considered the fourth layer of the vascular wall and contributes to the regulation of vascular reactivity in most vascular beds and most species. This review focuses on mechanisms of uterine artery reactivity and the role of PVAT in pregnancy‐induced maternal vascular adaptations, with an emphasis on the uterine circulation.

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Innervation of adipocytes is limited in mouse perivascular adipose tissue

Hanscom,

Morales-Soto,

Watts

et al. 2024

American Journal of Physiology-Heart and Circulatory Physiology

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Background: Perivascular adipose tissue (PVAT) regulates vascular tone by releasing anticontractile factors. These anticontractile factors are driven by processes downstream of adipocyte stimulation by norepinephrine; however, whether norepinephrine originates from neural innervation or other sources is unknown. The goal of this study was to test the hypothesis that neurons innervating PVAT provide the adrenergic drive to stimulate adipocytes in aortic and mesenteric perivascular adipose tissue (aPVAT, mPVAT), and white adipose tissue (WAT). Methods: Healthy male and female mice (8-13 weeks) were used in all experiments. Expression of genes associated with synaptic transmission were quantified by qPCR and adipocyte activity in response to neurotransmitters and neuron depolarization was assessed in AdipoqCre+;GCaMP5g-tdTf/WT mice. Immunostaining, tissue clearing, and transgenic reporter lines were used to assess anatomical relationships between nerves and adipocytes. Results: While synaptic transmission components genes are expressed in adipose tissues (aPVAT, mPVAT, WAT), strong nerve stimulation with electrical field stimulation does not significantly trigger calcium responses in adipocytes. However, norepinephrine consistently elicits strong calcium responses in adipocytes from all adipose tissues studied. Bethanechol induces minimal adipocyte responses. Imaging neural innervation using various techniques reveals that nerve fibers primarily run alongside blood vessels and rarely branch into the adipose tissue. Conclusion: While nerve fibers are associated with blood vessels in adipose tissue, they demonstrate limited anatomical and functional interactions with adjacent adipocytes, challenging the concept of classical innervation. These findings dispute the significant involvement of neural input in regulating PVAT adipocyte function and emphasize alternative mechanisms governing adrenergic-driven anticontractile functions of PVAT.

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Cyclooxygenase-dependent mechanisms mediate in part the anti-dilatory effects of perivascular adipose tissue in uterine arteries from pregnant rats

Cited by 4 publications

References 61 publications

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

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

Perivascular Adipose Tissue and Uterine Artery Adaptations to Pregnancy

Innervation of adipocytes is limited in mouse perivascular adipose tissue

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