Inhibitory Effects of Hydrogen on Proliferation and Migration of Vascular Smooth Muscle Cells via Down-Regulation of Mitogen/Activated Protein Kinase and Ezrin-Radixin-Moesin Signaling Pathways.

Abstract

This study examined how molecular hydrogen affects angiotensin II (Ang II)-driven proliferation and migration of vascular smooth muscle cells (VSMCs) in vitro, and abdominal aortic coarctation (AAC)-induced vascular hypertrophy in vivo. Hydrogen-rich medium (0.6–0.9 ppm) was applied 30 minutes before 10⁻⁷ M Ang II, with endpoints assessed at 24 hours. In the animal model, pure hydrogen gas (99.999%) was administered intraperitoneally at 1 ml/100 g/day for one week prior to AAC and continued for six weeks. Hydrogen reduced reactive oxygen species in Ang II-stimulated VSMCs, lowered 3-nitrotyrosine in vascular tissue, and decreased serum malondialdehyde. Phosphorylation of ERK1/2, p38 MAPK, JNK, and ezrin/radixin/moesin (ERM) proteins was also suppressed. These findings suggest that ROS-dependent MAPK and ERM signaling mediates the inhibitory effects of hydrogen on VSMC proliferation, migration, and vascular remodeling.

Mechanism

Hydrogen scavenges reactive oxygen species, thereby suppressing phosphorylation of ERK1/2, p38 MAPK, JNK, and ERM proteins, which reduces Ang II-induced VSMC proliferation and migration as well as AAC-induced vascular hypertrophy.