Valvular & structural heart disease
COL1A1-Enhanced CD44/SLC7A11 Interaction and Cystine Uptake Result in CD34 + Foam-Like Macrophage Accumulation in Transplant Arteriosclerosis
Authors' conclusion
This study has revealed previously uncharacterized foam-like macrophages in transplant arteriosclerosis, with COL1A1-enhanced amino acid metabolism modulating lipogenesis and foamy macrophage formation.
Study context
- Population
- Human chronic allograft vasculopathy specimens and mouse vascular allograft models
Methodological detailssingle-cell RNA sequencing, spatial transcriptomics, CD34+ lineage tracing, myeloid-specific Slc7a11 knockout mice
- Single-cell RNA sequencing
- Spatial transcriptomics
- CD34+ lineage tracing
- Myeloid-specific Slc7a11 knockout mice
Main finding
As reported in the abstract
- Novel proinflammatory foam-like macrophage phenotype identified in allograft arterial adventitia
- These macrophages primarily originate from bone marrow-derived CD34+ lineage cells, with heightened de novo lipogenesis and proinflammatory activity
- Lipogenesis driven by increased cystine uptake via enhanced membrane CD44-SLC7A11 complex, activating mTORC1-HIF-1α signaling
- Fibroblast-secreted COL1A1 anchors the complex to the cell membrane through direct interaction with CD44
- Blocking COL1A1, CD44 or SLC7A11 attenuated mTORC1-HIF-1α signaling, inflammation and lipogenesis in macrophages, and foam-like cell accumulation and intimal hyperplasia in allograft arteries
Original publication
COL1A1-Enhanced CD44/SLC7A11 Interaction and Cystine Uptake Result in CD34 + Foam-Like Macrophage Accumulation in Transplant Arteriosclerosis. Circulation. Published 4 August 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →