title: Glycyrrhizin, inhibitor of high mobility group box-1, attenuates monocrotaline-induced pulmonary hypertension and vascular remodeling in rats.
abstract: BACKGROUND
  High mobility group box-1 (HMGB1), a proinflammatory cytokine, plays a pivotal role in tissue remodeling and angiogenesis, both of which are crucial for the pathogenesis of pulmonary arterial hypertension. In this study, we explored the relationship between HMGB1 and pulmonary hypertension and whether glycyrrhizin, an inhibitor of HMGB1, attenuates disease progression in an animal model of pulmonary hypertension induced by monocrotaline sodium (MCT).
  
  
  METHODS
  After inducing pulmonary hypertension through a single subcutaneous injection of MCT (60 mg/kg) to Sprague-Dawley rats, we administered daily intraperitoneal injections of either glycyrrhizin (GLY, 50 mg/kg), an inhibitor of HMGB1, or saline (control) for either 4 or 6 weeks.
  
  
  RESULTS
  Expression levels of HMGB1 in serum increased from the second week after MCT injection and remained elevated throughout the experiment periods. Lung tissue levels of HMGB1 assessed by immunohistochemical staining at 4 weeks after MCT injection also increased. Chronic inhibition of HMGB1 by GLY treatment reduced the MCT-induced increase in right ventricular (RV) systolic pressure, RV hypertrophy (ratio of RV to [left ventricle + septum]), and pulmonary inflammation. MCT-induced muscularization of the pulmonary artery was also attenuated in the GLY-treated group. As assessed 6 weeks after MCT injection, the GLY-treated group exhibited increased survival (90% [18 of 20]) when compared with the control group (60% [12 of 20]; p =0.0027).
  
  
  CONCLUSIONS
  Glycyrrhizin, an inhibitor of HMGB1, attenuates pulmonary hypertension progression and pulmonary vascular remodeling in the MCT-induced pulmonary hypertension rat model. Further studies are needed to confirm the potential of HMGB1 as a novel therapeutic target for pulmonary hypertension.
authors.affiliation: Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University Health System, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752, Republic of Korea. psyang@yuhs.ac.
authors.forename: Pil-Sung
authors.initials: PS
authors.lastname: Yang
authors.affiliation: Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University Health System, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752, Republic of Korea. kimdhoon@yuhs.ac.
authors.forename: Dae-Hoon
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Departments of Microbiology, Yonsei University College of Medicine, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752, Republic of Korea. sinwhayj@naver.com.
authors.forename: Yong Joon
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University Health System, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752, Republic of Korea. tkddmss@yuhs.ac.
authors.forename: Sang-Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Departments of Nuclear Medicine, Yonsei University College of Medicine, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752, Republic of Korea. mdkwj@yuhs.ac.
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Kang
authors.affiliation: Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University Health System, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752, Republic of Korea. hjchang@yuhs.ac.|Severance Biomedical Science Institute, Yonsei University Health System, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752, Republic of Korea. hjchang@yuhs.ac.
authors.forename: Hyuk-Jae
authors.initials: HJ
authors.lastname: Chang
authors.affiliation: Departments of Microbiology, Yonsei University College of Medicine, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752, Republic of Korea. jsshin6203@yuhs.ac.|Severance Biomedical Science Institute, Yonsei University Health System, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752, Republic of Korea. jsshin6203@yuhs.ac.
authors.forename: Jeon-Soo
authors.initials: JS
authors.lastname: Shin
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D016686:Monocrotaline; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011014:Pneumonia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D066253:Vascular Remodeling / Q000187:drug effects*; D018497:Ventricular Dysfunction, Right / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D016278:Ventricular Function, Right / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D019332:Endothelin-1; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D019695:Glycyrrhizic Acid; D016686:Monocrotaline