title: Inhibition of neointimal hyperplasia in the rat carotid artery injury model by a HMGB1 inhibitor.
abstract: OBJECTIVE
  High mobility group box 1 protein (HMGB1) is expressed in atherosclerotic lesions. However, its role in vascular system is unknown. In this study, we explore whether the inhibition of HMGB1 attenuates neointimal formation in animal models.
  
  
  RESULTS
  Experiments were performed with VSMCs from thoracic aorta of SD rats in vitro, and a rat carotid artery balloon injury model in vivo. HMGB1 levels were increased after stimulation of angiotensin II (Ang II) and 10% serum in cultured VSMCs. HMGB1 inhibitor (glycyrrhizin) significantly inhibited the proliferation and migration of Ang II-treated VSMCs, which was accompanied with decreased oxidative stress and inflammation. The underlying mechanisms were related with the promotion of antioxidant systems activity and deactivation of p38 MAPK/NF-κB signaling pathway, respectively. Furthermore, inhibition of HMGB1 blunted Notch signaling pathway during VSMCs phenotypic transition, and correspondingly restored VSMCs differentiated phenotype under 10% serum stimulation. In vivo study, HMGB1 expression was elevated after artery injury. Meanwhile, glycyrrhizin treatment suppressed HMGB1 expression, which was accompanied with blunted inflammation and oxidative stress after 7 days of balloon injury. Moreover, the area of neointimal to media area ratio was significantly decreased in glycyrrhizin group compared with injury group at 14 days after balloon injury.
  
  
  CONCLUSIONS
  Inhibition of HMGB1 activity attenuated VSMCs activation and neointimal formation after carotid injury. Therefore, blockage of HMGB1 might represent a novel therapeutic strategy for vascular injury.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Changwu
authors.initials: C
authors.lastname: Xu
authors.forename: Sisi
authors.initials: S
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006965:Hyperplasia; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D058426:Neointima; D018384:Oxidative Stress / Q000187:drug effects; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002317:Cardiovascular Agents; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D018836:Inflammation Mediators; D016328:NF-kappa B; D051880:Receptors, Notch; D000804:Angiotensin II; D019695:Glycyrrhizic Acid; D048051:p38 Mitogen-Activated Protein Kinases