NPC-EXs Alleviate Endothelial Oxidative Stress and Dysfunction through the miR-210 Downstream Nox2 and VEGFR2...

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Neural progenitor cells (NPCs) offer protection against endothelial cell (EC) oxidative stress.
• Exosomes (EXs) mediate cellular benefits via microRNAs (miRs); miR-210 is a significant functional miR.

Purpose of the Study:

• To investigate the role of miR-210 in NPC-derived exosome (NPC-EX) protection against endothelial oxidative stress and dysfunction.
• To elucidate the molecular mechanisms underlying NPC-EXs' protective effects on endothelial cells.

Main Methods:

• NPCs were transfected to generate exosomes with altered miR-210 levels (control, scramble, inhibitor, mimic).
• The effects of these exosomes on angiotensin II (Ang II)-induced oxidative stress, apoptosis, and dysfunction in ECs were assessed.
• Key molecular markers including Nox2, ephrin A3, VEGF, and VEGFR2 phosphorylation were evaluated.

Main Results:

• Ang II induced oxidative stress, apoptosis, and dysfunction in ECs, with altered expression of Nox2 and VEGFR2.
• NPC-EXs with enhanced miR-210 (NPC-EXs^miR-210) attenuated Ang II-induced detrimental effects more effectively than control exosomes.
• NPC-EXs with inhibited miR-210 (NPC-EXs^anti-miR-210) showed reduced protective capacity, linked to changes in miR-210, ephrin A3, VEGF, and VEGFR2 signaling.

Conclusions:

• NPC-derived exosomes exert protective effects against Ang II-induced endothelial injury.
• miR-210 within NPC-EXs is a critical mediator of this protection.
• NPC-EXs regulate endothelial function by controlling Nox2/ROS and VEGF/VEGFR2 signaling pathways via miR-210.