Single-Cell RNA-Sequencing Reveals the Active Involvement of Macrophage Polarizations in Pulmonary Hypertension.
Single-Cell RNA-Sequencing Reveals the Active Involvement of Macrophage Polarizations in Pulmonary Hypertension.
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DOI：
10.1155/2022/5398157
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Wang, Liangxing
中科院分区：
文献类型：
--
作者：
Mao, Xulong;Li, Yaozhe;Yang, Rui;Wei, Jingqiu;Zhao, Zhucheng;Zhang, Ting;OuYang, Mingli;Liu, Xiaoling;Liu, Can;Xu, Hao;Huang, Xiaoying;Wang, Liangxing
持续的低氧会引发肺动脉压力的进行性升高，并导致严重的肺部疾病。巨噬细胞在肺动脉高压的发展过程中起着重要作用。然而，肺高压早期巨噬细胞的极化状态尚不清楚。与传统的测序方法不同，单细胞测序可以准确区分细胞类型，更好地了解细胞之间的关系。在这项研究中，我们通过单细胞RNA测序在小鼠缺氧模型中研究了巨噬细胞在肺动脉高压中的极化，并在肺动脉高压患者中进行了验证。我们发现，在小鼠模型中，间歇性暴露在低氧条件下可以导致产生比M1型巨噬细胞更多的M2型巨噬细胞。通过分析肺动脉高压患者的肺组织进行进一步的验证分析，发现与疾病相关的M2巨噬细胞的数量显著增加。在本研究中，证实了参与肺动脉高压的巨噬细胞的主动抗炎反应，提示针对巨噬细胞对M2型极化的干预可能是减轻慢性肺炎症、肺血管重构和动脉压的潜在途径。因此，研究与缺氧相关的巨噬细胞极化有助于我们更好地了解疾病的发病机制，制定有效的预防策略和方法。
Sustained hypoxia can trigger a progressive rise in pulmonary artery pressure and cause serious pulmonary diseases. Macrophages play important roles along the progression of pulmonary hypertension. However, the state of macrophage polarization during the early stage of pulmonary hypertension is unclear. Unlike traditional sequencing method, single-cell sequencing can accurately distinguish among cell types and better understand cell-to-cell relationships. In this study, we investigated the polarization of macrophages in pulmonary hypertension via single-cell RNA-sequencing in a mice hypoxia model, which was then validated in patients with pulmonary hypertension. We identified that the intermittent exposure to hypoxic conditions could lead to the production of more M2-type macrophages than M1-type macrophages in a mouse model. Further validation analysis was performed by analyzing lung tissue of patients with pulmonary hypertension, revealing that the number of disease-associated M2 macrophages was substantially increased. In this study, the active anti-inflammatory response of macrophage involved in pulmonary hypertension has been identified, suggesting that intervention against the polarization of macrophages to the M2 type may be a potential way to reduce chronic pulmonary inflammation, pulmonary vascular remodeling, and artery pressure. Thus, investigation of macrophage polarization associated with hypoxia could help us better understand disease mechanism and craft effective prevention strategies and approaches.
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