Macrophage-derived inflammation promotes pulmonary vascular remodeling in hypoxia-induced pulmonary arterial hypertension mice

Hong Liu; Yuxiang Wang; Qingqing Zhang; Chuanchuan Liu; Yougang Ma; Pan Huang; Rili Ge; Lan Ma

doi:10.1016/j.imlet.2023.10.005

Macrophage-derived inflammation promotes pulmonary vascular remodeling in hypoxia-induced pulmonary arterial hypertension mice

Immunol Lett. 2023 Nov:263:113-122. doi: 10.1016/j.imlet.2023.10.005. Epub 2023 Oct 22.

Authors

Hong Liu¹, Yuxiang Wang¹, Qingqing Zhang², Chuanchuan Liu³, Yougang Ma¹, Pan Huang¹, Rili Ge¹, Lan Ma⁴

Affiliations

¹ Research Center for High Altitude Medicine, Qinghai university, Xining, Qinghai, China; Key Laboratory of the Ministry of High Altitude Medicine, Qinghai university, Xining, Qinghai, China; Key Laboratory of Applied Fundamentals of High Altitude Medicine, (Qinghai-Utah Joint Key Laboratory of Plateau Medicine), Qinghai university, Xining, Qinghai, China; Laboratory for High Altitude Medicine of Qinghai Province, Qinghai university, Xining, Qinghai, China.
² Research Center for High Altitude Medicine, Qinghai university, Xining, Qinghai, China; Key Laboratory of the Ministry of High Altitude Medicine, Qinghai university, Xining, Qinghai, China; Key Laboratory of Applied Fundamentals of High Altitude Medicine, (Qinghai-Utah Joint Key Laboratory of Plateau Medicine), Qinghai university, Xining, Qinghai, China; Laboratory for High Altitude Medicine of Qinghai Province, Qinghai university, Xining, Qinghai, China; Affiliated Hospital of Qinghai University, Xining, QingHai, China.
³ Affiliated Hospital of Qinghai University, Xining, QingHai, China.
⁴ Research Center for High Altitude Medicine, Qinghai university, Xining, Qinghai, China; Key Laboratory of the Ministry of High Altitude Medicine, Qinghai university, Xining, Qinghai, China; Key Laboratory of Applied Fundamentals of High Altitude Medicine, (Qinghai-Utah Joint Key Laboratory of Plateau Medicine), Qinghai university, Xining, Qinghai, China; Laboratory for High Altitude Medicine of Qinghai Province, Qinghai university, Xining, Qinghai, China. Electronic address: judyml-325@163.com.

PMID: 37875238
DOI: 10.1016/j.imlet.2023.10.005

Abstract

The role of inflammation in pulmonary hypertension is gradually gaining increasing research attention. However, no previous study has evaluated the characteristics of inflammation during chronic hypoxia-induced pulmonary hypertension. Therefore, the aim of this study was to investigate the characteristics of the inflammatory process involved in hypoxia-induced pulmonary hypertension in mice. The current study evaluated from day 4 to day 28 of hypoxia, the PAAT and PAAT/PET decreased, accompanied by pulmonary vascular remodeling and right ventricular hypertrophy, as well as increased numbers of CD68 macrophages. The expression of the pro-inflammatory factors IL-1β and IL-33 increased, but decreased on day 28. The expression of IL-12 increased from day 4 to day 28, whereas that of the anti-inflammatory factor IL-10 in lung tissue decreased. Furthermore, the expression of the IL-33/ST2 signaling pathway also increased over time under hypoxic conditions. In conclusion, pulmonary artery remodeling in HPH mice worsens progressively in a time-dependent manner, with inflammatory cell infiltration predominating in the early stage and pulmonary vascular remodeling occurring in the later stage.

Keywords: Hypoxic pulmonary hypertension; Immunomodulation; Immunotherapy; Macrophages.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Hypertension, Pulmonary* / complications
Hypertension, Pulmonary* / metabolism
Hypoxia
Inflammation / complications
Interleukin-33
Macrophages / metabolism
Mice
Pulmonary Arterial Hypertension* / complications
Vascular Remodeling

Substances

Interleukin-33