Iron, arginine, and redox metabolism in peripheral blood mononuclear cells distinguishes sickle cell disease and pulmonary hypertension - PubMed
2 days ago
- #pulmonary hypertension
- #metabolomics
- #sickle cell disease
- Pulmonary hypertension (PH) is a severe complication of sickle cell disease (SCD), but not all SCD patients develop PH.
- Multi-omic analysis of PBMCs from SCD, PH, SCD-PH, and healthy controls revealed distinct metabolic and immune signatures.
- SCD PBMCs showed elevated intracellular iron and mitochondrial suppression.
- PH PBMCs exhibited dysregulated arginine and creatine metabolism, affecting nitric oxide pathways.
- SCD-PH PBMCs displayed amplified hemoglobin/iron handling, oxidative stress, and immune activation.
- Unsupervised clustering confirmed discrete disease phenotypes with overlap between SCD and SCD-PH.
- Histological evidence linked iron accumulation in perivascular macrophages to pulmonary vascular pathology in SCD-PH.
- PBMC profiling offers a novel tool for mechanistic insight, patient stratification, and biomarker discovery.