Single-Cell RNA-Sequencing Reveals the Active Involvement of Macrophage Polarizations in Pulmonary Hypertension

Abstract

Background. 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. Methods. 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. Results. 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. Conclusions. 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.

Ythdf2 promotes pulmonary hypertension by suppressing Hmox1-dependent anti-inflammatory and antioxidant function in alveolar macrophages

“…Macrophages have remarkable phenotypic plasticity that enables them to efficiently respond to a variety of stimuli by generating three macrophage populations that can be broadly categorized as classically activated (M1), alternatively activated (M2), and anti-inflammatory (regulatory) macrophages [ 11 ]. Of these subtypes, M2 macrophages were reported to be involved in the development of PH and other lung disorders due to their ability to promote fibrosis, injury repair and angiogenesis [ 12 ]. Furthermore, recent studies demonstrated that the recruitment of alternatively activated macrophage in the early stages of PH were critical for later PVR [ 13 ].…”