Macrophages: key conductors behind perivascular inflammation and vascular remodeling in hypoxia-induced pulmonary hypertension.

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.