PIEZO1 Mediates Apoptosis of Endothelial Cells via Enhancing HMGA2 Expression Under Simulated Microgravity

Area of Science:

• Cardiovascular Physiology
• Cell Biology
• Space Medicine

Background:

• Microgravity causes cardiovascular deconditioning, with endothelial cell apoptosis as a key factor.
• Mechanisms linking microgravity to endothelial cell apoptosis are not well understood.

Purpose of the Study:

• Investigate the role of mechanosensitive ion channels in microgravity-induced endothelial cell apoptosis.
• Elucidate the specific molecular pathways involved.

Main Methods:

• Upregulation of PIEZO1 in human umbilical vein endothelial cells (HUVECs) under simulated microgravity.
• Functional studies on PIEZO1 activation and its effect on apoptosis.
• Proteomic analysis after PIEZO1 knockdown.
• Assessment of calcium influx and HMGA2 expression.
• HMGA2 knockdown to evaluate its role in apoptosis.

Main Results:

• PIEZO1 expression and activation increase under simulated microgravity, promoting endothelial apoptosis.
• PIEZO1 activation leads to calcium influx and elevated HMGA2 expression.
• HMGA2 knockdown significantly reduces microgravity-induced endothelial apoptosis.

Conclusions:

• A novel PIEZO1-Ca2+-HMGA2 signaling axis is identified as critical for microgravity-induced endothelial apoptosis.
• This pathway provides mechanistic insights into cardiovascular adaptation to spaceflight.
• The identified axis presents potential therapeutic targets for countermeasures against spaceflight-induced deconditioning.