Oral Acid-Activated Hydrogen-Producing Nanoparticles Reduce Aortic Dissection Progression via RhoA/ROCK Inhibition in Mice

Aortic dissection (AD) is a life-threatening condition with a high mortality rate. Oxidative stress and endothelial and vascular smooth muscle cell migration contribute to AD pathogenesis. Herein, we investigated the therapeutic potential of hydrogen (H₂), delivered via magnesium diboride nanosheets (MBNs), in a murine model of β-aminopropionitrile-induced AD. This treatment significantly improved survival rate and reduced AD progression, as evidenced by improved aortic wall structure and reduced false lumen formation. Transcriptomic analysis indicated modulation of the RhoA/ROCK pathway, confirmed using Western blotting, immunohistochemistry, and immunofluorescence, which showed significant downregulation of RhoA and ROCK2 after 28 days of treatment (P < 0.05). These findings suggest that hydrogen released from MBNs attenuates AD progression through reactive oxygen species scavenging and RhoA/ROCK pathway inhibition.