Relationship between phospholipase D activation and endothelial vasomotor dysfunction in rabbit aorta

Area of Science:

• Vascular biology
• Endothelial function
• Signal transduction

Background:

• Lysophosphatidylcholine (lysoPC) is known to cause endothelial vasomotor dysfunction.
• The specific signaling pathways mediating lysoPC's vascular effects are not fully understood.
• Previous studies indicated lysoPC stimulates phospholipase D (PLD) in endothelial cells, but its role in vascular dysfunction was unclear.

Purpose of the Study:

• To investigate the role of phospholipase D (PLD) in lysophosphatidylcholine (lysoPC)-induced endothelial vasomotor dysfunction in isolated rabbit aorta.
• To determine if PLD activation is a common pathway for endothelial dysfunction induced by various agents.

Main Methods:

• Isolated rabbit aorta preparations were used to assess vasorelaxation responses to acetylcholine.
• Vascular phospholipase D (PLD) activity was measured in response to lysophosphatidylcholine (lysoPC) and other stimuli.
• The effect of a protein kinase C (PKC) inhibitor on lysoPC-induced dysfunction was evaluated.

Main Results:

• Lysophosphatidylcholine (lysoPC) stimulated vascular PLD activity and inhibited endothelium-dependent vasorelaxation in a concentration-dependent manner.
• Inhibition of vasorelaxation by lysoPC was not affected by a protein kinase C (PKC) inhibitor.
• Other lysophospholipids and orthovanadate also stimulated PLD activity and induced endothelial dysfunction, with a strong correlation between PLD stimulation and the extent of dysfunction (r2 = 0.88).

Conclusions:

• The phospholipase D (PLD) signal transduction pathway plays a significant role in lysophosphatidylcholine (lysoPC)-induced endothelial vasomotor dysfunction.
• PLD activation is implicated in the endothelial dysfunction caused by various agents, not just lysophospholipids.
• These findings highlight PLD as a potential therapeutic target for vascular dysfunction.