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Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
Plasma from hypertensive pregnancy patients induce endothelial dysfunction even under atheroprotective shear stress
Sarah Viana-Mattioli1,2, Miriam Helena Fonseca-Alaniz2, Iguaracy Pinheiro-de-Sousa2,3
1Department of Biophysics and Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista (UNESP), Distrito Rubião Júnior, Botucatu, São Paulo, SP, Brazil.
Insights
Preeclampsia and gestational hypertension impact endothelial cells differently under varying blood flow conditions. Preeclampsia plasma induced pro-inflammatory and antioxidant responses, while gestational hypertension plasma promoted cell proliferation under laminar shear stress.
Area of Science:
- Cardiovascular Biology
- Reproductive Medicine
- Molecular Genetics
Background:
- Preeclampsia (PE) is a significant maternal health concern linked to endothelial dysfunction (ED).
- Previous research has not fully explored the role of blood flow patterns, specifically laminar (LSS) and oscillatory (OSS) shear stress, in PE-related ED.
- Placental factors released under oxygen deprivation are implicated in triggering ED.
Purpose of the Study:
- To investigate the impact of plasma from healthy pregnant women (HP), gestational hypertension (GH), and PE patients on human coronary artery endothelial cells (HCAECs).
- To analyze the gene expression profiles of HCAECs under both LSS and OSS conditions when exposed to different plasma types.
- To elucidate how shear stress influences endothelial cell responses to hypertensive pregnancy states.
Main Methods:
- Incubation of HCAECs with plasma from HP, GH, and PE subjects.
- Exposure of treated HCAECs to controlled laminar shear stress (LSS) and oscillatory shear stress (OSS) conditions.
- Global gene expression analysis (transcriptome profiling) to identify differential gene expression patterns.
Main Results:
- Laminar shear stress (LSS) induced a unique transcriptional profile in endothelial cells exposed to plasma.
- Oscillatory shear stress (OSS) resulted in similar transcriptomes regardless of the plasma source.
- Under LSS, GH plasma led to a proliferative endothelial cell profile, while PE plasma induced pro-inflammatory and antioxidant profiles compared to HP plasma.
Conclusions:
- Shear stress patterns significantly modulate endothelial cell gene expression in response to plasma from pregnancies complicated by hypertension.
- Both PE and GH can contribute to endothelial dysfunction, even under atheroprotective LSS conditions.
- PE-derived plasma demonstrated a more pronounced effect on endothelial cell transcriptome compared to GH plasma under LSS.
Abstract:
Preeclampsia (PE) is a challenge in maternal healthcare due to its complex nature, characterized by high blood pressure, protein in the urine, and damage to various organs. There is evidence linking PE to endothelial dysfunction (ED), triggered by substances released from an oxygen-deprived placenta. Previous in vitro studies have not considered the impact of in vivo elements, such as the different patterns of blood flow, and laminar (LSS) vs. oscillatory (OSS) shear stress, on the development of ED. We investigated the impact of plasma from healthy pregnant women (HP), subjects with gestational hypertension (GH), and PE patients on global gene expression of human coronary endothelial cells (HCAECs) under LSS and OSS. Our findings revealed a unique transcriptional profile of endothelial cells induced by plasma incubation in LSS. Notably, OSS resulted in similar transcriptomes irrespective of plasma treatment. Under LSS, GH plasma resulted in a proliferative profile, whereas PE plasma was linked to pro-inflammatory and antioxidant profiles compared to HP plasma. Our findings demonstrate that shear stress levels influence the endothelial cell transcriptome in response to plasma from hypertensive pregnancy patients. Both PE and GH can induce endothelial dysfunction under atheroprotective LSS, with a more significant effect observed with PE-derived plasma.
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