Ion channel Piezo1 activation aggravates the endothelial dysfunction under a high glucose environment

Area of Science:

• Cardiovascular Biology
• Endothelial Cell Biology
• Diabetic Complications

Background:

• Diabetes mellitus frequently leads to vasculopathy, a major complication.
• Endothelial cells are crucial for vascular regulation and are sensitive to mechanical forces.
• Hyperglycemia-induced endothelial damage is a key factor, but the role of mechanosensitive signaling is unclear.

Purpose of the Study:

• To investigate the role of the mechanosensitive channel Piezo1 in hyperglycemia-induced endothelial injury.
• To determine the therapeutic potential of targeting Piezo1 in diabetic vasculopathy.

Main Methods:

• Generated vascular endothelial-specific Piezo1 knockout mice.
• Induced hyperglycemia using Streptozotocin.
• Assessed endothelial cell proliferation, migration, and function in vitro under high glucose conditions.
• Evaluated oxidative stress markers and inflammatory responses in aortic tissues.

Main Results:

• Piezo1 deficiency in endothelial cells alleviated hyperglycemia-induced endothelial cell apoptosis and inflammation.
• Knockout of Piezo1 reduced thoracic aortic wall thickness and tunica media damage, improving endothelial function.
• Piezo1 activation exacerbated oxidative stress and endothelial dysfunction via the Ca2+-CaMKII-Nrf2 pathway.
• Piezo1 deficiency restored antioxidant enzyme activity and reduced lipid peroxidation markers.

Conclusions:

• Piezo1 plays a significant role in high glucose-induced oxidative stress and endothelial dysfunction.
• Targeting Piezo1 offers a promising therapeutic avenue for mitigating endothelial damage in diabetic vasculopathy.