Aspirin Improves Uterine Artery Function in Hypercholesterolemic Preeclampsia

Area of Science:

• Obstetrics and Gynecology
• Cardiovascular Research
• Pharmacology

Background:

• High cholesterol in pregnancy (HC-PE) increases preeclampsia risk, with impaired uterine artery function linked to the toll-like receptor 4 (TLR4)/prostaglandin H synthase 1 (PGHS1) pathway.
• Oxidized low-density lipoprotein (oxLDL) levels increase in HC-PE, potentially activating TLR4 and the scavenger receptor LOX-1 (lectin-like oxLDL receptor-1), but this remains unconfirmed.

Purpose of the Study:

• To investigate the effects of low-dose aspirin on uterine artery function in a rat model of HC-PE.
• To determine if aspirin modulates the TLR4/PGHS1 and oxLDL/TLR4/LOX-1 pathways in HC-PE.

Main Methods:

• A rat model of HC-PE was established using a high-cholesterol diet.
• Rats received either placebo or low-dose aspirin during pregnancy.
• Uterine artery function, blood flow, placental weight, and molecular pathway activation were assessed.

Main Results:

• Low-dose aspirin reduced elevated uterine artery blood flow velocity and placental weights in HC-PE rats.
• Aspirin normalized impaired endothelium-dependent vasodilation in HC-PE uterine arteries.
• Inhibition of TLR4, PGHS1, or LOX-1 ex vivo also improved vasodilation; oxLDL exposure further impaired vasodilation, partly via TLR4/LOX-1, an effect blocked by aspirin.

Conclusions:

• Low-dose aspirin effectively improves uterine artery endothelial function in HC-PE.
• Aspirin's beneficial effects are likely mediated by suppressing the TLR4/LOX-1/PGHS1 pathway.