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 starvationinduced 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.

Key words: pulmonary arterial hypertension; myelin and lymphocyte protein; vascular remodeling; pulmonary artery smooth muscle cells; nuclear factor-κB