EnFUSiasm for Healing: Ultrasound Neuromodulation in PAH

Pulmonary arterial hypertension (PAH) is a progressive disease of irreversibly remodeled distal pulmonary arteries, elevated pulmonary vascular resistance, and subsequent development of right heart failure and premature death.The integral role of inflammation in the pathogenesis of PAH is based on the established higher risk of developing PAH among individuals with autoimmune or infectious disorders 1 .Preclinical studies show that immune upregulation contributes to vascular and cardiac damage, followed by the uncontrolled cell proliferation in pulmonary vessels, right ventricular hypertrophy, and fibrosis.The spectrum of tested experimental models exacerbating the inflammatory milieu, including cytokine overexpression, induces or promotes PAH, while interventions targeting cytokine-driven inflammatory pathways have demonstrated promising protective effects 2,3 .Recent advantages in imaging, single-cell transcriptomics, and computational analytics improved our ability to delineate PAH-induced shifts in the pulmonary and cardiac landscapes of resident immune cells.Multiple studies report an enrichment of perivascular CD68+ macrophages, an expansion of pro-inflammatory CD4+ Th17 and CD8+ T cells, and deficiency of anti-inflammatory regulatory T cells (Tregs) in both human and experimental PH.Nevertheless, these studies have also discovered the high intricacy of the immune cell network, which complicates targeting inflammation in PAH 4 .