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

Yuxia Huang; Ji Zhang; Qinhua Zhao; Xiaoyi Hu; Hui Zhao; Shang Wang; Lan Wang; Rong Jiang; Wenhui Wu; Jinming Liu; Ping Yuan; Sugang Gong

doi:10.1016/j.hjc.2023.10.004

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

Hellenic J Cardiol. 2023 Nov 7:S1109-9666(23)00195-1. doi: 10.1016/j.hjc.2023.10.004. Online ahead of print.

Authors

Yuxia Huang¹, Ji Zhang², Qinhua Zhao¹, Xiaoyi Hu¹, Hui Zhao³, Shang Wang¹, Lan Wang¹, Rong Jiang¹, Wenhui Wu¹, Jinming Liu⁴, Ping Yuan⁵, Sugang Gong⁶

Affiliations

¹ Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200000, China.
² Department of Lung Transplantation, First Affiliated Hospital, School of Medical, Zhejiang University, Hangzhou 310000, China.
³ Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200000, China; Institute of Bismuth Science, University of Shanghai for Science and Technology, Shanghai 200000, China.
⁴ Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200000, China. Electronic address: jinmingliu@tongji.edu.cn.
⁵ Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200000, China. Electronic address: pandyyuan@tongji.edu.cn.
⁶ Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200000, China. Electronic address: gongsugang@tongji.edu.cn.

PMID: 37940001
DOI: 10.1016/j.hjc.2023.10.004

Abstract

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.

Keywords: ApoA-I; High-density lipoprotein; Inflammation; Proteomics; Pulmonary arterial hypertension.