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

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

doi:10.21037/atm-22-1221

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

Ann Transl Med. 2022 Apr;10(8):446. doi: 10.21037/atm-22-1221.

Authors

Huilin Peng¹, Ming Wei¹, Lianjing Huang¹, Yaqin Yan¹, Qing Li¹, Sujuan Li¹, Yichi Wu¹, Yuan Gao¹, Ying Xing¹, Xiaoping Luo¹

Affiliation

¹ Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

Background: To explore whether maternal obesity inhibits placental angiogenesis through down-regulation of Sirtuin 1/Peroxisome proliferator-activated receptor-γ coactivator-1α (SIRT1/PGC-1α) signaling pathway.

Methods: In a rat model of pre-pregnancy obesity, rats were sacrificed at embryonic day (E)18.5. Maternal characteristics were measured. Placentas were collected to observe the pathological changes and angiogenesis using hematoxylin-eosin (HE) staining and platelet endothelial cell adhesion molecule-1 [PECAM-1/CD31 (CD31)] immunohistochemical (IHC) staining, and the expression of the SIRT1/PGC-1α signaling pathway was also analyzed using western blotting and quantitative real-time polymerase chain reaction (qPCR). In in vitro experiments, human umbilical vein endothelial cells (HUVECs) were incubated under high fat conditions. We activated and inhibited the SIRT1/PGC-1α signaling pathway to determine the proliferation, angiogenic tube formation, and migration capacity of endothelial cells. Cell counting kit-8 (CCK-8) assays, tubule formation assays, and scratch wound-healing migration assays were also performed.

Results: In vivo results showed that compared with the control group, the high-fat diet (HFD) group were heavier and their plasma triglyceride and total cholesterol contents were higher. The ratio of fetal weight to placental weight was reduced in the HFD group compared to the control group. In the HFD group, placental angiogenesis was decreased, and the SIRT1/PGC-1α signaling pathway was down-regulated compared with that in the control group. The results of in vitro experiments showed that SRT1720 reduced SIRT1/PGC-1α and vascular endothelial growth factor (VEGFA) expression inhibition induced by high fat stress, while EX-527 increased SIRT1/PGC-1α and VEGFA expression inhibition. Compared with the control group, maternal obesity impaired placental angiogenesis and reduced the proliferation and migration of HUVECs.

Conclusions: The results suggest that maternal obesity impairs placental angiogenesis. They also provide experimental evidence that activation of the SIRT1/PGC-1α signaling pathway improves angiogenesis in vitro.

Keywords: SIRT1/PGC-1α pathway; angiogenesis; maternal obesity; placenta.