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Glycyrrhizin, inhibitor of high mobility group box-1, attenuates monocrotaline-induced pulmonary hypertension and vascular remodeling in rats.

 Pil Sung Yang  ;  Dae Hoon Kim  ;  Yong Joon Lee  ;  Sang Eun Lee  ;  Won Jun Kang  ;  Hyuk Jae Chang  ;  Jeon Soo Shin 
 RESPIRATORY RESEARCH, Vol.15 : 148, 2014 
Journal Title
Issue Date
Animals ; Antihypertensive Agents/pharmacology* ; Arterial Pressure/drug effects* ; Cell Proliferation/drug effects ; Cells, Cultured ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Endothelin-1/metabolism ; Glycyrrhizic Acid/pharmacology* ; HMGB1 Protein/antagonists & inhibitors* ; HMGB1 Protein/metabolism ; Humans ; Hypertension, Pulmonary/chemically induced ; Hypertension, Pulmonary/metabolism ; Hypertension, Pulmonary/pathology ; Hypertension, Pulmonary/physiopathology ; Hypertension, Pulmonary/prevention & control* ; Hypertrophy, Right Ventricular/metabolism ; Hypertrophy, Right Ventricular/physiopathology ; Hypertrophy, Right Ventricular/prevention & control ; Male ; Monocrotaline* ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/metabolism ; Muscle, Smooth, Vascular/pathology ; Pneumonia/metabolism ; Pneumonia/physiopathology ; Pneumonia/prevention & control ; Pulmonary Artery/drug effects* ; Pulmonary Artery/metabolism ; Pulmonary Artery/pathology ; Pulmonary Artery/physiopathology ; Rats, Sprague-Dawley ; Time Factors ; Vascular Remodeling/drug effects* ; Ventricular Dysfunction, Right/metabolism ; Ventricular Dysfunction, Right/physiopathology ; Ventricular Dysfunction, Right/prevention & control ; Ventricular Function, Right/drug effects
High mobility group box-1 (HMGB1) ; Pulmonary hypertension ; Pulmonary vascular remodeling ; Glycyrrhizin ; Inflammation
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Kang, Won Jun(강원준) ORCID logo https://orcid.org/0000-0002-2107-8160
Kim, Dae Hoon(김대훈) ORCID logo https://orcid.org/0000-0002-9736-450X
Shin, Jeon Soo(신전수) ORCID logo https://orcid.org/0000-0002-8294-3234
Yang, Pil Sung(양필성)
Lee, Sang-Eun(이상은) ORCID logo https://orcid.org/0000-0001-6645-4038
Lee, Yong Joon(이용준)
Chang, Hyuk-Jae(장혁재) ORCID logo https://orcid.org/0000-0002-6139-7545
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