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

被引:1
|
作者
Huang, Yuxia [1 ]
Zhang, Ji [2 ]
Zhao, Qinhua [1 ]
Hu, Xiaoyi [1 ]
Zhao, Hui [1 ,3 ]
Wang, Shang [1 ]
Wang, Lan [1 ]
Jiang, Rong [1 ]
Wu, Wenhui [1 ]
Liu, Jinming [1 ]
Yuan, Ping [1 ]
Gong, Sugang [1 ]
机构
[1] Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Cardiopulm Circulat, 507 Zhengmin Rd, Shanghai 200000, Peoples R China
[2] Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Lung Transplantat, Hangzhou 310000, Peoples R China
[3] Univ Shanghai Sci & Technol, Inst Bismuth Sci, Shanghai 200000, Peoples R China
基金
中国国家自然科学基金; 上海市自然科学基金;
关键词
Proteomics; Pulmonary; arterial hypertension; High-density; lipoprotein; ApoA-I; Inflammation; DENSITY-LIPOPROTEIN CHOLESTEROL; APOA-I; HDL; REGIONS; CELLS;
D O I
10.1016/j.hjc.2023.10.004
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 antiinflammatory 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. (Hellenic Journal of Cardiology 2024;80:31-46) (c) 2023 Hellenic Society of Cardiology. Publishing services by Elsevier B.V. This is an open access article under the CC BY- NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
引用
收藏
页码:31 / 46
页数:16
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