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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Lipopolysaccharide exposure during pregnancy leads to aortic dysfunction in offspring rats
Shanyu Zhao1, Haigang Zhang2, Dayan Cao1
1Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
Insights
Prenatal inflammation from Lipopolysaccharide (LPS) exposure causes aortic dysfunction in offspring rats. This is linked to reduced connexin 37 (Cx37) expression and increased nuclear factor-kappa B (NF-κB) activation.
Area of Science:
- Cardiovascular Science
- Developmental Biology
- Immunology
Background:
- Prenatal exposure to Lipopolysaccharide (LPS) is known to induce hypertension in adult offspring.
- Understanding the long-term effects of prenatal inflammation on cardiovascular health is crucial.
Purpose of the Study:
- To investigate the impact of prenatal inflammation on aortic morphology and function in offspring rats.
- To assess the susceptibility of these offspring to cardiovascular diseases.
- To explore the role of connexins and NF-κB signaling in these changes.
Main Methods:
- Pregnant rats were exposed to LPS or saline during gestation.
- Aortic ring reactivity and histopathology were analyzed in 12-week-old offspring.
- Expression of connexins (Cx37, Cx40, Cx43, Cx45) and NF-κB pathway components were quantified at protein and mRNA levels.
Main Results:
- Prenatal LPS exposure resulted in aortic morphological abnormalities and impaired vascular reactivity in offspring.
- A significant decrease in aortic connexin 37 (Cx37) protein and mRNA expression was observed.
- Increased levels of nuclear factor-kappa B (NF-κB) and phospho-IκBα, with decreased IκBα, indicated NF-κB pathway activation.
- Treatment with pyrrolidine dithiocarbamate (PDTC) reversed LPS-induced effects.
Conclusions:
- Reduced Cx37 expression in the aorta is a key factor in the aortic dysfunction observed in offspring exposed to prenatal LPS.
- This dysfunction is associated with the activation of the NF-κB signaling pathway.
- Targeting NF-κB activation may offer therapeutic strategies for mitigating prenatal inflammation-induced cardiovascular damage.
Background:
Prenatal exposure to Lipopolysaccharide (LPS) produces hypertension in adult offspring rats. The present study was to explore the effects of prenatal inflammation on morphological and functional changes in the aorta from offspring rats and to further assess its susceptibility to cardiovascular diseases.
Methods And Results:
Pregnant rats were treated intraperitoneally on gestation Days 8, 10 and 12 with saline, LPS (0.79 mg/kg), or pyrrolidine dithiocarbamate (PDTC, 100 mg/kg)+LPS, respectively. Aortic ring reactivity and histopathological alteration were analyzed in offspring at the age of 12 weeks. The detections of connexin (Cx) 37, Cx40, Cx43, and Cx45, including immunofluorescent patterns, protein levels and mRNA expression in the aorta, were performed as well. Furthermore, the expressions of Nuclear factor (NF)-κB (p65), IκBα, phospho-IκBα and IκBβ were determined. The results showed that prenatal LPS exposure leads to morphological abnormalities and impaired aortic reactivity in offspring. Prenatal LPS exposure also decreased the protein and mRNA expression of Cx37 in the aorta from offspring rats. NF-κB and phospho-IκBα levels were both increased, IκBα level, however, was decreased in the aorta of offspring from the maternal LPS exposure compared to the controls. Simultaneously, PDTC treatment markedly reversed the action of LPS.
Conclusions:
Decreased expression of Cx37 contributed to the aortic dysfunction of prenatal LPS exposure offspring, which should be associated with NF-κB activation.
