Abstract 13102: Inhibition of Hmgb1 Attenuates Smooth Muscle Cell Proliferation And Balloon Injury-Induced Neointimal Hyperplasia
BACKGROUND HMGB1, a DNA-binding protein and cytokine, is expressed by endothelial cells, vascular smooth muscle cells (VSMCs) and macrophages in atherosclerotic lesions. However, its role in vascular system is unknown. In this study, we explore whether the inhibition of HMGB1 attenuates VSMCs activation and neointimal formation in animal models.
METHODS AND RESULTS Experiments were performed with VSMCs from thoracic aorta of Sprague-Dawley rats in vitro, and a rat carotid artery balloon injury model in vivo. HMGB1 levels were increased 3 hours after stimulation of angiotensin II (Ang II) in cultured VSMCs and in balloon injury of the rat carotids at 7 days on mRNA levels. HMGB1 inhibitor (glycyrrhizin (Gly)) significantly inhibited the proliferation and migration of Ang II-treated VSMCs in a dose (10, 50, 100 μmol/L)-dependent manner. Gly (100 μmol/L) also suppressed the expression of IL-6 and MCP-1 in VSMCs in the presence of Ang II. In addition, HMGB1 inhibition with Gly reduced the phosphorylation of the MAP kinases ERK1/2 and p38 MAPK in Ang II-stimulated VSMCs. Furthermore, the carotid arteries from SD rats were injured by balloon catheter, followed by intraperitoneal injection with Gly (80 mg/kg/d) or normal saline. After 14 days treatments, the area of neointimal to media area ratio was significantly decreased (0.17±0.09 in Gly group vs. 1.08±0.15 in control group, p < 0.05). Alpha-VSMC-positive cell population, as well as the incidence of proliferating cells labeled with proliferating cell nuclear antigen, was also down-regulated in neointimal in Gly group compared with control group (p < 0.05).
CONCLUSION Inhibition of HMGB1 activity attenuated VSMCs activation and neotimal formation after carotid injury. Therefore, blockage of HMGB1 might represent a novel therapeutic strategy for vascular injury.
- © 2011 by American Heart Association, Inc.