Hydropersulfides promote angiogenesis and preserve vascular function

Area of Science:

• Biochemistry
• Physiology
• Cell Biology

Background:

• Hydropersulfides (RSSH) are emerging redox signaling molecules in mammalian cells.
• The physiological roles of RSSH, particularly in angiogenesis, are largely unknown.
• Investigating RSSH is difficult due to their inherent instability and reactivity.

Purpose of the Study:

• To investigate the role of hydropersulfides (RSSH) in vascular angiogenesis.
• To elucidate the signaling mechanisms by which RSSH influences angiogenesis.
• To examine the relationship between RSSH, nitric oxide (NO) signaling, and vascular tone.

Main Methods:

• Utilized thiol- and enzyme-activated RSSH donors for controlled RSSH release.
• Employed mutant mouse models deficient in cysteinyl-tRNA synthetase/cysteine persulfide synthase (CARS2/CPERS).
• Analyzed the Akt-eNOS and NO-cGMP signaling pathways.

Main Results:

• Demonstrated that RSSH promotes angiogenesis through the CARS2/CPERS signaling axis.
• Showed activation of the Akt-eNOS and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway by RSSH.
• Confirmed that nitric oxide (NO) signaling in resistance vessels requires an intact CARS2/CPER2 pathway.

Conclusions:

• Hydropersulfides (RSSH) play a significant role in regulating angiogenesis.
• The CARS2/CPERS signaling axis is crucial for RSSH-mediated angiogenesis.
• RSSH influences vascular tone and nitric oxide signaling in blood vessels.