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.

Scientific Reports
|February 7, 2025
PubMed

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.

Related Concept Videos

Hormonal Regulation01:33

Hormonal Regulation

The renin-aldosterone system is an endocrine system which guides the renal absorption of water and electrolytes, thus managing blood pressure and osmoregulation. Activation of the system begins in the kidneys with a small cluster of cells adjacent to the afferent and efferent blood vessels of the renal corpuscle. As the nephrons are filtering blood, juxtaglomerular cells monitor blood pressure. If they detect a decrease in pressure, they release the hormone renin into the bloodstream.
32.8K
Hypertension and Regulation of Blood Pressure01:18

Hypertension and Regulation of Blood Pressure

Hypertension, the most common cardiovascular disease, is diagnosed through repeated measurements of elevated blood pressure. Its risks, including damage to the kidney, heart, and brain, are directly proportional to blood pressure levels. Starting from 115/75 mm Hg, the risk of cardiovascular disease doubles with each increment of 20/10 mm Hg. The diagnosis relies on blood pressure measurements, not on patient symptoms, as hypertension is often asymptomatic until end-organ damage is imminent or...
1.9K
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
131