Oxysterols, cholesterol biosynthesis, and vascular endothelial cell monolayer barrier function

Area of Science:

• Biochemistry
• Cardiovascular Biology
• Cell Biology

Background:

• Oxysterols are cholesterol oxidation derivatives found in foods.
• Certain oxysterols can compromise vascular endothelial cell barrier function.
• This compromise may play a role in the initiation of atherosclerotic lesion formation.

Purpose of the Study:

• To investigate the relationship between cholesterol synthesis inhibition by oxysterols and their effect on endothelial barrier function.
• To determine if oxysterol-induced changes in barrier function correlate with suppressed cholesterol biosynthesis.
• To explore the mechanisms by which oxysterols impact endothelial cells.

Main Methods:

• Exposure of cultured vascular endothelial cell monolayers to various oxysterols and pure cholesterol.
• Measurement of trans-endothelial albumin transfer to assess barrier function.
• Quantification of cholesterol biosynthesis inhibition by oxysterols and mevinolin.

Main Results:

• All tested oxysterols increased albumin transfer and inhibited cholesterol biosynthesis in a dose- and time-dependent manner.
• Pure cholesterol had no effect on barrier function or cholesterol biosynthesis.
• A poor correlation was observed between increased albumin transfer and cholesterol biosynthesis inhibition.
• Mevinolin significantly inhibited cholesterol synthesis but did not increase albumin transfer.
• Cholestan-3 beta,5 alpha,6 beta-triol markedly elevated albumin transfer while only partially inhibiting cholesterol synthesis.

Conclusions:

• Oxysterol-induced changes in endothelial barrier function are likely mediated by mechanisms other than cholesterol biosynthesis inhibition.
• Pure cholesterol does not affect endothelial barrier function or cholesterol synthesis.
• These findings suggest novel pathways involved in atherosclerosis development related to oxysterol exposure.