Optogenetic intervention to the vascular endothelium

Area of Science:

• Cardiovascular Biology
• Optogenetics
• Endothelial Cell Physiology

Background:

• The endothelium regulates vascular tone via vasoactive substances, but its control mechanisms, particularly the role of membrane potential, remain unclear.
• Selective intervention in endothelial cell membrane potentials is crucial for understanding their function in vascular diseases.

Purpose of the Study:

• To develop and validate a novel optogenetic approach for selectively manipulating endothelial cell membrane potentials in situ.
• To investigate the functional consequences of optogenetically induced endothelial cell depolarization on vascular tone.

Main Methods:

• Generation of transgenic mice expressing channelrhodopsin (ChR) in endothelial cells using the Cre-loxP system and cdh5 promoter.
• Detection of ChR expression via YFP fluorescence in various endothelium-lining tissues.
• Optostimulation of endothelial cells in isolated organs (heart, kidney) and dissociated cell cultures.

Main Results:

• Optostimulation of endothelial cells evoked inward currents and depolarization in vitro.
• Optostimulation induced rapid, robust, and sustained vasoconstriction in isolated perfused hearts and kidneys.
• The observed vasoconstriction was independent of ET-1A and TXA2 receptor pathways.

Conclusions:

• Optogenetics provides an effective tool for intervening in vascular endothelium function.
• Optogenetic stimulation of endothelial cells leads to significant vasoconstriction, independent of known receptor pathways.
• This approach offers a new method for studying endothelial cell-mediated vascular regulation.