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

Respiratory Research

Jeon-Soo Shin²  Hyuk-Jae Chang²  Won Jun Kang³  Sang-Eun Lee¹  Yong Joon Lee⁴  Dae-Hoon Kim¹  Pil-Sung Yang¹ 

[1] Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University Health System, 50 Yonsei-ro Seodaemun-gu, Seoul 120-752, Republic of Korea;Severance Biomedical Science Institute, Yonsei University Health System, 50 Yonsei-ro Seodaemun-gu, Seoul 120-752, Republic of Korea;Departments of Nuclear Medicine, Yonsei University College of Medicine, 50 Yonsei-ro Seodaemun-gu, Seoul 120-752, Republic of Korea;Departments of Microbiology, Yonsei University College of Medicine, 50 Yonsei-ro Seodaemun-gu, Seoul 120-752, Republic of Korea

关键词: Inflammation;    Glycyrrhizin;    Pulmonary vascular remodeling;    Pulmonary hypertension;    High mobility group box-1 (HMGB1);   

Others  :  1137236
DOI  :  10.1186/s12931-014-0148-4

 received in 2014-02-01, accepted in 2014-11-10,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Yang et al.; licensee BioMed Central Ltd.

【 图 表 】

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