NF-κB inhibitor improves pulmonary vascular remodeling by reversing LPS-induced down-regulation of BMPRII.
- Author:
Mei-Jun ZHOU
1
;
Yan-Jiang XING
2
;
Jun YANG
3
Author Information
1. State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS), School of Basic Medicine, Peking Union Medical College (PUMC), Beijing 100005, China.
2. State Key Laboratory of Medical Molecular Biology, Department of Cell Biology, Institute of Basic Medical Sciences, CAMS, School of Basic Medicine, PUMC, Beijing 100005, China.
3. Department of Physiology, and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Bone Morphogenetic Protein Receptors, Type II;
Down-Regulation;
Endothelial Cells/metabolism*;
Humans;
Hypertension, Pulmonary/drug therapy*;
Lipopolysaccharides;
NF-kappa B/metabolism*;
Rats;
Rats, Sprague-Dawley;
Vascular Remodeling
- From:
Acta Physiologica Sinica
2020;72(5):541-550
- CountryChina
- Language:Chinese
-
Abstract:
The occurrence and development of pulmonary arterial hypertension (PAH) is closely related to the genetic mutation of bone morphogenetic protein receptor type II (BMPRII) encoding gene and the inflammatory response mediated by nuclear factor κB (NF-κB) pathway. This paper was aimed to investigate the effect of NF-κB pathway inhibitors on lipopolysaccharide (LPS)-induced pulmonary artery endothelial cell injury. Human pulmonary artery endothelial cells were treated with 1 μg/mL of LPS. The expression levels of BMPRII and interleukin-8 (IL-8) were detected by Western blot and qPCR. The rat PAH model was established by intraperitoneal (i.p.) injection of monocrotaline (MCT). The expression levels of BMPRII and IL-8 in pulmonary artery endothelial cells were detected by immunofluorescence staining. Cardiac hemodynamic changes and pulmonary vascular remodeling were detected in the MCT-PAH model rats. The results showed that LPS caused down-regulation of BMPRII expression and up-regulation of IL-8 expression in human pulmonary artery endothelial cells. NF-κB inhibitor BAY11-7082 (10 μmol/L) reversed the effect of LPS. In the pulmonary artery endothelial cells of MCT-PAH model, BMPRII expression was down-regulated, IL-8 expression was up-regulated, weight ratio of right ventricle to left ventricle plus septum [RV/(LV+S)] and right ventricular systolic pressure (RVSP) were significantly increased, cardiac output (CO) and tricuspid annular plane systolic excursion (TAPSE) were significantly reduced, and pulmonary vessel wall was significantly thickened. BAY11-7082 (5 mg/kg, i.p., 21 consecutive days) reversed the above changes in the MCT-PAH model rats. These results suggest that LPS down-regulates the expression level of BMPRII through NF-κB signaling pathway, promoting the occurrence and development of PAH. Therefore, the NF-κB pathway can be used as a potential therapeutic target for PAH.
