Role of myelin and lymphocyte protein in regulating pulmonary artery smooth muscle cell proliferation and apoptosis in pulmonary hypertension.
10.12122/j.issn.1673-4254.2022.10.19
- Author:
Jin Jun LIU
1
;
Qing Qing LI
2
;
Chao Chao ZENG
1
;
Yue Xiang WANG
1
;
Qing Tian HU
1
;
Hong Ju WANG
1
;
Shi Li WU
1
Author Information
1. Department of Cardiology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
2. Bengbu Medical College, Bengbu 233030, China.
- Publication Type:Journal Article
- Keywords:
myelin and lymphocyte protein;
nuclear factor-κB;
pulmonary arterial hypertension;
pulmonary artery smooth muscle cells;
vascular remodeling
- MeSH:
Humans;
Pulmonary Artery;
Hypertension, Pulmonary;
Myelin Sheath/metabolism*;
Apoptosis;
Myocytes, Smooth Muscle;
Vascular Remodeling/genetics*;
Cell Proliferation;
Hypoxia/metabolism*;
Lymphocytes
- From:
Journal of Southern Medical University
2022;42(10):1572-1577
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the role of myelin and lymphocyte protein (MAL) in pulmonary hypertension (PAH).
METHODS:Blood samples were collected from 50 patients with PAH (PAH group) and 50 healthy individuals for detection of plasma MAL expression using ELISA.According to the echocardiographic findings, the patients were divided into moderate/severe group (n=18) and mild group (n=32), and the correlation between MAL protein level and the severity of PAH was analyzed.In a pulmonary artery smooth muscle cell model of PAH with hypoxia-induced abnormal proliferation, the effects of mal gene knockdown and overexpression on cell growth, proliferation and starvation-induced apoptosis were observed; the changes in NK-κB signaling pathway in the transfected cells were detected to explore the molecular mechanism by which MAL regulates PAMSC proliferation and apoptosis.
RESULTS:The plasma level of MAL was significantly higher in patients with PAH than in healthy individuals (P < 0.05), and the patients with moderate/severe PAH had significantly higher MAL level than those with mild PAH (P < 0.001).In PAMSCs, exposure to hypoxia significantly increased the mRNA and protein expression levels of MAL (P < 0.05), and MAL knockdown obviously inhibited hypoxia-induced proliferation and promoted starvation-induced apoptosis of the PAMSCs (P < 0.05).Knocking down mal significantly inhibited the activation of NK-κB signaling pathway that participated in regulation of PAMSC proliferation (P < 0.05).
CONCLUSION:The plasma level of MAL is elevated in PAH patients in positive correlation with the disease severity.MAL knockdown inhibits abnormal proliferation and promotes apoptosis of PAMSCs by targeted inhibition of the NF-κB signaling pathway to improve vascular remodeling in PAH.
