Macrophages: key conductors behind perivascular inflammation and vascular remodeling in hypoxia-induced pulmonary hypertension
Year: 2025
Type: article
Abstract: Pulmonary hypertension (PH) encompasses a heterogenous group of disorders with the common feature of increased pulmonary arterial pressures. Patients with PH associated with lung disease and/or hypoxia undergo immune-mediated vascular remodeling that includes thickening of the muscular layer surrounding arteries and arterioles. In this issue of the JCI, Kumar and colleagues examined the role of interstitial macrophages in a model of high-altitude PH. Resident interstitial macrophages increased, proliferated, and expressed CCL2, a monocyte chemoattractant ligand. There was also a rise in CCR2+ macrophages expressing thrombospondin-1, which is known to activate vascular remodeling through TGF-β. Blocking monocyte recruitment partially reduced hypoxic PH, and corticosteroid treatment effectively reduced CCL2 expression and CCR2+ monocyte recruitment. Further, plasma samples collected from individuals ascending from low to high altitudes showed increased thrombospondin-1 and TGF-β levels, which were reduced with dexamethasone. These findings reveal interstitial macrophage populations as potential therapeutic targets in hypoxic PH.
DOI: 10.1172/jci190957
Author: Edda Spiekerkoetter
Institutions: Stanford Medicine, Stanford University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: Targeting Novel BMPR2 modifiers in Pulmonary Hypertension with Repurposed Drugs, Understanding and targeting molecular as well as structural events governing right ventricular adaptation, failure and recovery in pulmonary hypertension using repurposed drugs, Developmental Heterogeneity of Pulmonary Endothelial Phenotype at Single Cell Resolution, Lipid Peroxidation-Induced Mitochondrial Injury Inhibits Vascular Function in Single Ventricle Congenital Heart Disease, Understanding and targeting molecular and cellular events responsible for pulmonary arteriovenous malformation development, growth and regression, What triggers RV Fiber Re-Orientation in response to RV pressure overload, and what is its Consequence on Inter-Ventricular Decoupling?
OpenAlex ID: W4408491174