Impact of reduced apolipoprotein A-I levels on pulmonary arterial hypertension

OBJECTIVE: The significance of apolipoprotein A-I (ApoA-I) is the anti-inflammatory functional component of high-density lipoprotein, which needs to be further studied in relation to pulmonary arterial hypertension (PAH). This study aimed to identify the predictive value of ApoA-1 on the risk and prognosis of PAH, as well as the underlying anti-inflammatory mechanism. METHODS: Proteomic analysis was conducted on lung tissue from 6 PAH patients and 4 lung donors. Prediction of risk and mortality risk factors associated with PAH in 343 patients used logistic analysis and Cox regression analysis, respectively. The protective function of ApoA-I was assessed in human pulmonary arterial endothelial cells (HPAEC), while its anti-inflammatory function was evaluated in THP-1 macrophages. RESULTS: In the lung tissues of patients with PAH, 168 differentially expressed proteins were associated with lipid metabolism according to GO and KEGG enrichment analysis. A protein-protein interaction network identified ApoA-I as a key protein associated with PAH. Lower ApoA-I levels were independent risk factors for PAH and displayed a stronger predictive value for PAH mortality. Plasma interleukin 6 (IL-6) levels were positively correlated with risk stratification and were higher in PAH patients with lower ApoA-I levels. ApoA-I was downregulated in the lung tissues of monocrotaline (MCT) -induced rats. ApoA-I could reduce the IL-6-induced pro-proliferative and pro-migratory abilities of HPAEC and inhibit the secretion of IL-6 from macrophages, which is compromised under hypoxic conditions. CONCLUSION: Our study identified the significance of ApoA-I as a biomarker for predicting the survival outcome of PAH patients, which might relate to its altered anti-inflammatory properties.