Maternal obesity inhibits placental angiogenesis by down-regulating the SIRT1/PGC-1α pathway

Peng, Huilin; Wei, Ming Hui; Huang, Lianjing; Yan, Yaqin; Li, Qing; Li, Sujuan; Wu, Yichi; Gao, Yuan; Xing, Ying; Li, Xiaoping

doi:10.21037/atm-22-1221

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…Overexpression of SIRT1 has been shown to alleviate joint inflammation in RA [ 45 ]. Interestingly, SIRT1 has a dual effect on blood vessel formation, with SIRT1 deficiency inhibiting this process [ 46 ], and SIRT1 activation inhibiting RA angiogenesis through the MAPK and Rho/Rock pathway [ 11 , 47 ]. Our study revealed significantly decreased levels of SIRT1 in CIA rats and TNF-α induced FLS, which were upregulated by CSO treatment.…”

Section: Discussionmentioning

confidence: 99%

Coix seed oil alleviates synovial angiogenesis through suppressing HIF-1α/VEGF-A signaling pathways via SIRT1 in collagen-induced arthritis rats

Xu,

Kong,

Ren

et al. 2023

Chin Med

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Background Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by symmetric arthritis. Coix Seed Oil (CSO) has been shown to reduce inflammation in collagen induced arthritis (CIA) rats. However, the effect of CSO on synovial angiogenesis in RA is unknown. In this study, we aimed to explore whether CSO could inhibit RA synovial angiogenesis and elucidate the underlying mechanisms. Methods CIA rat models were established and subjected to different doses of CSO treatments for four weeks in vivo. Arthritis index, paw swelling, and weight were recorded to assess clinical symptoms. Hematoxylin and Eosin staining, Safarnin O fast green staining, Micro-CT, Immunohistochemical, and Immunofluorescence (IF) staining were performed to examined changes in synovial and joint tissues. The serum HIF-1α and VEGF-A levels were evaluated through enzyme-linked immunosorbent assay. Fibroblast-like synoviocytes (FLS) of rats was stimulated with tumor necrosis factor-α (TNF-α) for developing inflammatory model in vitro. Optimal concentrations of CSO and TNF-α for stimulation were measured through Cell Counting Kit-8 test. Wound healing and Transwell migration experiments were employed to determine FLS migratory ability. IF staining was performed to assess HIF-1α nuclear translocation in FLS. Protein levels of SIRT1, HIF-1α, VEGF-A, and CD31 were assessed through Western blot. The isolated aortic rings were induced with recombinant rat VEGF-A 165 (VEGF-A165) to observe the CSO inhibitory impact on angiogenesis ex vivo. Results CSO attenuated the progression of arthritis in CIA rats, mitigated histopathological deterioration in synovial and joint tissues, significantly inhibited immature vessels labeled with CD31+/αSMA−, and reduced the micro-vessels in VEGF-A165 induced aortic rings. Moreover, it upregulated SIRT1 protein levels in CIA rats and TNF-α induced FLS, but decreased HIF-1α and VEGF-A protein levels. Furthermore, CSO inhibited the migration ability and HIF-1α nuclear translocation of TNF-α induced FLS. Finally, suppressing SIRT1 levels in TNF-α induced FLS enhanced their migration ability, HIF-1α nuclear translocation, and the protein levels of HIF-1α, VEGF-A, and CD31, whereas the inhibitory effect of CSO on TNF-α induced FLS was severely constrained. Conclusions This study indicates that CSO can alleviate synovial angiogenesis through suppressing HIF-1α/VEGF-A signaling pathways via SIRT1 in CIA rats.

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Section: Discussionmentioning

confidence: 99%

Coix seed oil alleviates synovial angiogenesis through suppressing HIF-1α/VEGF-A signaling pathways via SIRT1 in collagen-induced arthritis rats

Xu,

Kong,

Ren

et al. 2023

Chin Med

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“…SIRT1-null mice had smaller placentas and abnormalities in both the LZ and JZ [ 53 ]. Another study showed that maternal overnutrition reduces SIRT1 expression in placental tissue [ 54 ]. Thus, it can be speculated that SIRT1 may be a key player in the protection of FA against placental dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Dietary Folic Acid Supplementation Attenuates Maternal High-Fat Diet-Induced Fetal Intrauterine Growth Retarded via Ameliorating Placental Inflammation and Oxidative Stress in Rats

Zhang

Wang

et al. 2023

Nutrients

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The placenta is particularly susceptible to inflammation and oxidative stress, leading to placental vascular dysfunction and placental insufficiency, which is associated with fetal intrauterine growth restriction (IUGR). It is unknown whether folic acid (FA) supplementation can alleviate high-fat diet-induced IUGR in rats by improving placental function. In this study, pregnant rats were randomized into one of four diet-based groups: (1) control diet (CON), (2) control diet supplemented with FA, (3) high-fat diet (HFD), and (4) high-fat diet supplemented with FA (HFD + FA). Dams were sacrificed at gestation day 18.5 (GD18.5). The results indicated that dietary FA supplementation normalized a maternal HFD-induced decrease in fetal weight. The decrease in placental efficiency, labyrinth zone (LZ) area, blood sinusoid area, vascular density, and the levels of angiogenesis factors induced by a maternal HFD were alleviated by the addition of FA, suggesting that FA supplementation can alleviate placental vascular dysplasia. Furthermore, FA supplementation increased the protein expressions of SIRT1, inhibited NF-κB transcriptional activation, attenuated the levels of NF-κB/downstream pro-inflammatory cytokines, induced Nrf2 activation, and increased downstream target protein expression. In conclusion, we found that dietary FA supplementation during pregnancy could improve maternal HFD-induced IUGR by alleviating placental inflammation and oxidative stress, which may be associated with the regulation of SIRT1 and its mediated NF-κB and Nrf2 signaling pathways.

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“…In animal models, maternal obesity has been induced by feeding experimental diets containing high levels of sugar and/or fat (Table 2 ). In mice, diet‐induced obesity can compromise labyrinthine zone development, with reductions in the relative volume of the labyrinthine, decreased vessel formation, surface area and blood sinusoids, and increased barrier thickness in association with reduced fetal weight (Kretschmer et al., 2020 ; Napso et al., 2022 ; Peng et al., 2022 ; Song et al., 2018 ; Stuart et al., 2018 ). However, the specific nature of the effect can depend on fetal sex, with morphological defects often more pronounced in female versus male placentas (Napso et al., 2022 ; Stuart et al., 2018 ).…”

Section: Adaptations Of the Placenta During Normal Pregnancymentioning

confidence: 99%

Placental adaptations supporting fetal growth during normal and adverse gestational environments

Sferruzzi‐Perri

López-Tello

Salazar‐Petres

2022

Experimental Physiology

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The placenta is vital for mammalian development and a key determinant of life-long health. It is the interface between the mother and fetus and is responsible for transporting the nutrients and oxygen a fetus needs to develop and grow. Alterations in placental formation and function, therefore, have consequences for fetal growth and birthweight, which in turn determine perinatal survival and risk of non-communicable diseases for the offspring in later postnatal life. However, the placenta is not a static organ. As this review summarizes, research from multiple species has demonstrated that placental formation and function alter developmentally to the needs of the fetus for substrates for growth during normal gestation, as well as when there is greater competition for substrates in polytocous species and monotocous species with multiple gestations. The placenta also adapts in response to the gestational environment, integrating information about the ability of the mother to provide nutrients and oxygen with the needs of the fetus in that prevailing environment.In particular, placental structure (e.g. vascularity, surface area, blood flow, diffusion distance) and transport capacity (e.g. nutrient transporter levels and activity) respond to suboptimal gestational environments, namely malnutrition, obesity, hypoxia and maternal ageing. Mechanisms mediating developmentally and environmentally induced homeostatic responses of the placenta that help support normal fetal growth include imprinted genes, signalling pathways, subcellular constituents and fetal sexomes. Identification of these placental strategies may inform the development of therapies for complicated human pregnancies and advance understanding of the pathways underlying poor fetal outcomes and their consequences for health and disease risk.

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Maternal obesity inhibits placental angiogenesis by down-regulating the SIRT1/PGC-1α pathway

Cited by 5 publications

References 43 publications

Coix seed oil alleviates synovial angiogenesis through suppressing HIF-1α/VEGF-A signaling pathways via SIRT1 in collagen-induced arthritis rats

Coix seed oil alleviates synovial angiogenesis through suppressing HIF-1α/VEGF-A signaling pathways via SIRT1 in collagen-induced arthritis rats

Dietary Folic Acid Supplementation Attenuates Maternal High-Fat Diet-Induced Fetal Intrauterine Growth Retarded via Ameliorating Placental Inflammation and Oxidative Stress in Rats

Placental adaptations supporting fetal growth during normal and adverse gestational environments

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