Acetylcholine released by endothelial cells facilitates flow-mediated dilatation

Area of Science:

• Vascular biology
• Endothelial cell signaling
• Mechanotransduction

Background:

• The endothelium regulates vascular function through responses to stimuli like shear stress.
• The precise mechanisms of flow sensing and signal transduction in the endothelium are not fully understood.
• Acetylcholine (ACh) sensitivity in the endothelium is known, but its physiological role is unclear.

Purpose of the Study:

• To investigate the mechanisms of flow-mediated endothelial calcium signaling.
• To determine the role of acetylcholine (ACh) in endothelial responses to blood flow.
• To elucidate the signaling pathway from flow to endothelial cell activation.

Main Methods:

• Imaging endothelial calcium signaling in intact arteries under flow conditions.
• Investigating the release mechanism of ACh from endothelial cells.
• Analyzing the role of organic cation transporters and mitochondrial acetyl-CoA production.

Main Results:

• Endothelial cells release ACh in response to blood flow (shear stress).
• This flow-induced ACh acts in an autocrine manner to trigger endothelial calcium release.
• ACh release is non-vesicular, occurring via organic cation transporters, and involves mitochondrial acetyl-CoA.

Conclusions:

• Acetylcholine (ACh) is an autocrine signaling molecule released by endothelial cells in response to flow.
• Endothelial ACh release mediates flow-induced calcium signaling and artery relaxation.
• This study identifies a novel role for ACh in endothelial mechanotransduction.