CCR2+ macrophage density was significantly higher in compensated right ventricular failure compared with control and decompensated RV failure, indicating distinct subsets in adaptive remodeling.
Observational (n=15)
No
Distinct macrophage subpopulations characterize different stages of right ventricular failure, with CCR2+ macrophages enriched in adaptive remodeling and CD163+ macrophages trending higher in maladaptive remodeling.
Abstract Rationale Right ventricular (RV) dysfunction is a strong independent predictor of survival across diverse forms of pulmonary hypertension (PH) and heart disease. The pathophysiological mechanisms underlying RV failure remain incompletely characterized, particularly the biological distinctions between compensated and decompensated RV adaptation, and the contribution of inflammatory cells to this process. Macrophages play essential roles in maintaining homeostasis, regulating immune responses, and orchestrating repair after injury across all organs. In the heart, they can coordinate adaptive remodeling during stress and while persistent activation can drive maladaptive remodeling. We hypothesized that RV failure in PH is characterized by a higher density of macrophages compared to non-diseased, control right ventricles. We further hypothesized that distinct RV macrophage subsets are associated with adaptive and maladaptive remodeling. Methods Human RV tissue samples were obtained from autopsy cases or biopsies from a well-phenotyped biobank maintained at the Québec Heart and Lung Institute (Université Laval). Tissue collection and use were approved by the institutional ethics committee; all subjects provided informed consent. Five samples were chosen for each clinical category: control without RV failure, compensated RV failure, and decompensated RV failure due to end-stage pulmonary arterial hypertension. Formalin-fixed, paraffin-embedded sections were immunostained for CD68 (pan-macrophage marker), CD163 (resident macrophage marker, binding of hemoglobin-haptoglobin complexes), and C-C motif chemokine receptor 2 (CCR2, recruited macrophage marker) and imaged using the Vectra Polaris system. Automated tissue segmentation and quantification were performed with inForm® and imageJ software, respectively. Results There was a trend toward higher CD68+ macrophage density in all RV failure groups when compared to control RV. CCR2+ macrophage density was significantly higher in compensated RV failure compared with both control RV and decompensated RV failure. There was also a trend toward higher CD163+ macrophage density in decompensated RV failure compared to control RV. Conclusion Our results support the hypothesis that RV macrophages are increased in RV failure and that RV macrophage subpopulations differ between compensated and decompensated RV failure. While CCR2+ macrophages were significantly increased in adaptive RV remodeling, CD163+ macrophages showed a trend toward enrichment in maladaptive RV remodeling. These findings suggest that selective modulation or depletion of macrophage subsets could offer a novel therapeutic strategy to promote RV adaptation and prevent progression to RV failure in pulmonary hypertension. This abstract is funded by: ATS Early Career Investigator Award in Pulmonary Vascular Disease
Sangani et al. (Fri,) conducted a observational in Right ventricular failure (n=15). Compensated and decompensated RV failure vs. Control without RV failure was evaluated on Macrophage density (CD68+, CD163+, CCR2+). CCR2+ macrophage density was significantly higher in compensated right ventricular failure compared with control and decompensated RV failure, indicating distinct subsets in adaptive remodeling.