Pulmonary endarterectomy reversed right ventricular histological and transcriptional abnormalities in patients with chronic thromboembolic pulmonary hypertension, highlighting the role of extracellular matrix genes like SERPINE1, IL7R, and ANKRD1.
Cohort (n=102)
Does pulmonary endarterectomy reverse transcriptomic and structural right ventricular remodeling in patients with chronic thromboembolic pulmonary hypertension?
Pulmonary endarterectomy in CTEPH patients induces reverse structural and transcriptomic remodeling of the right ventricle, highlighting key ECM and cytoskeletal pathways.
Chronic thromboembolic pulmonary hypertension (CTEPH) leads to progressive right ventricular (RV) dysfunction. Pulmonary endarterectomy (PEA) is an established treatment for these patients; however, the molecular mechanisms underlying RV remodeling and recovery remain poorly understood. Here we show that RNA sequencing and histological analysis of RV free wall and septal biopsies from patients with CTEPH reveal extracellular matrix enrichment and cytoskeletal remodeling before PEA. These changes were consistent across an exploratory and confirmatory cohort. Post-PEA samples showed reversal of both histological and transcriptional abnormalities. Key signaling molecules-ANKRD1, IL7R and SERPINE1-were implicated in fibrotic and proliferative pathways, as confirmed in human tissues and experimental models. Our findings identify a reversible gene expression and structural remodeling signature in the RV, linking hemodynamic unloading with molecular recovery. These insights suggest potential therapeutic targets to modulate maladaptive RV remodeling in CTEPH and improve outcomes beyond surgical intervention.
Jafari et al. (Fri,) conducted a cohort in Chronic thromboembolic pulmonary hypertension (CTEPH) (n=102). Pulmonary endarterectomy (PEA) vs. Pre-PEA baseline and healthy controls was evaluated on Transcriptomic and structural remodeling changes in the right ventricle and septum. Pulmonary endarterectomy reversed right ventricular histological and transcriptional abnormalities in patients with chronic thromboembolic pulmonary hypertension, highlighting the role of extracellular matrix genes like SERPINE1, IL7R, and ANKRD1.