Inhalation of hydrogen gas reduces exacerbations of acute aortic dissection in mice.

Abstract

Acute aortic dissection (AAD) is a life-threatening vascular condition in which inflammatory processes drive disease progression and complications including rupture. Using a murine AAD model established by β-aminopropionitrile pretreatment combined with continuous angiotensin II infusion, male C57BL/6J mice were exposed to 2% H2 gas or control gas for 24 hours. H2 inhalation improved 24-hour survival and spontaneous locomotor activity without altering systolic blood pressure. Aortic rupture frequency and false lumen expansion were both reduced. Plasma IL-6 and G-CSF concentrations declined significantly, and MMP-9 and CXCL1 showed decreasing trends. Within the aortic wall, MMP-9 and CXCL1 expression—particularly in Ly-6B.2-positive regions—was diminished, and the number of Ly-6B.2-positive cells correlated positively with false lumen area. In bone marrow, the AAD-associated reduction in CD11b+Ly-6G+ neutrophils was significantly attenuated by H2 inhalation. Oxidative stress markers in the aortic wall were also reduced. These results suggest that 2% H2 gas inhalation limits AAD exacerbation through modulation of neutrophil-mediated inflammation and oxidative stress.

Mechanism

H2 inhalation reduces circulating IL-6 and G-CSF, suppresses MMP-9 and CXCL1 expression in the aortic wall, decreases neutrophil (Ly-6B.2-positive cell) infiltration, and attenuates oxidative stress, collectively limiting false lumen expansion and aortic rupture in AAD.