Maternal high-fat diet during pregnancy promotes aortic endothelial to mesenchymal transition in offspring
Aim To study the effect of maternal high-fat diet during pregnancy on endothelial to mesenchymal transition of aortic vessels in adult offspring.Methods The pregnant mice were randomly divided into normal diet group and high-fat diet group,and the offspring mice were fed normally for 16 weeks after the mother gave birth.Western blot and RT-qPCR were used to detect the expression and transcription of related proteins,and immunofluorescence and im-munohistochemical staining were used for pathological analysis.Results Compared with the offspring of maternal nor-mal diet during pregnancy,the expressions of vascular inflammatory factors,macrophage infiltration,monocyte-endothelium adhesion were significantly increased in the offspring of maternal high-fat diet(OHF)during pregnancy(P<0.05).Vas-cular endothelial nitric oxide synthase(eNOS)activity,nitric oxide(NO)level were dramatically reduced(P<0.05).Immunofluorescence results showed reduced endothelial cell marker CD31 and increased mesenchymal marker α-smooth muscle actin(α-SMA)in OHF.Western blot analysis further confirmed the results,which showed that maternal high fat diet reduced vascular endothelial-cadherin(VE-cadherin)and CD31 and increased α-SMA and Vimentin in the offspring(P<0.05).The maternal high fat diet increased the extracellular matrix protein disposition and transforming growth factor beta(TGF-β)/Smad signaling in endothelium(P<0.05).Moreover,the maternal high fat diet reduced Kruppel-like factor 2(KLF2)expression by 76%in mRNA level and 59%in protein level(P<0.05).Conclusion Maternal high-fat diet during pregnancy lead to a transition of endothelial to mesenchyme in the offspring aorta.The results provide a clue for prevention of vascular disease in early stage.
high-fat dietendothelial to mesenchymal transitionKruppel-like factor 2micematernal pregnancyoffspring