Modulation of vascular ATP diphosphohydrolase by fatty acids

Area of Science:

• Biochemistry
• Cell Biology
• Vascular Biology

Background:

• Endothelial cells (EC) have thromboregulatory mechanisms potentially altered by activation or injury.
• Vascular ATP-diphosphohydrolase (ATPDase) on EC regulates hemostasis and platelet reactivity by hydrolyzing extracellular ATP/ADP to AMP.

Purpose of the Study:

• To investigate how exogenous saturated and unsaturated fatty acids modulate EC-associated ATPDase activity in vitro.
• To determine if fatty acids influence EC viability and protect ATPDase activity against oxidative stress.

Main Methods:

• Cultured EC were supplemented with various saturated, monounsaturated, and polyunsaturated fatty acids.
• ATPDase activity was measured in EC cultures.
• EC viability was assessed with fatty acid supplementation.
• ATPDase activity was measured after exposure to reactive oxygen intermediates in EC pre-treated with oleic acid.

Main Results:

• Fatty acid supplementation did not significantly alter EC growth but enhanced viability with oleic acid, butyrate, and eicosapentaenoic acid.
• EC cultures supplemented with saturated or monounsaturated fatty acids (oleic acid) showed significantly increased ATPDase activity.
• Exposure to polyunsaturated fatty acids resulted in a substantial decrease in ATPDase activity.
• Exogenous oleic acid protected EC ATPDase activity from loss induced by reactive oxygen intermediates.

Conclusions:

• Endothelial ATPDase activity is regulated by exogenous fatty acids, affecting vascular hemostasis.
• Mechanisms involve alterations in EC membrane phospholipid composition, influencing responses to oxidative stress.