Clin Rheumatol. 2026 May 1. doi: 10.1007/s10067-026-08140-9. Online ahead of print.
ABSTRACT
OBJECTIVE: To investigate the role of CD34-high endothelial cells (CD34hi_ECs) and fibroblast growth factor-2 (FGF2) signaling in the pathological vasa vasorum angiogenesis and inflammatory progression of Takayasu arteritis (TAK).
METHODS: Single-cell RNA sequencing (scRNA-seq) and immunohistochemical analyses of aortic walls from three TAK patients and three controls were performed to evaluate CD34hi_ECs and FGF2 expression. Serum cytokines from 48 TAK patients and 24 healthy controls were measured by cytometric bead array.
RESULTS: ScRNA-seq of human aortic tissues revealed a marked expansion of CD34hi_ECs in TAK lesions (97.6% vs. 2.4% in controls; p < 0.001). CD34hi_ECs exhibited enrichment in biological processes related to vascular remodeling, leukocyte adhesion, and the MAPK signaling pathway. Serum FGF2 levels were significantly elevated in TAK patients and positively correlated with multiple pro-inflammatory cytokines, including G-CSF, CCL2, IL-6, IL-17, and IFN-γ. ScRNA-seq and immunohistochemistry identified selective overexpression of FGF2 in vasa vasorum endothelial cells in TAK, accompanied by upregulated FGFR1 expression and increased expression of genes associated with the downstream MAPK/ERK and PI3K/AKT signaling pathways in CD34hi_ECs.
CONCLUSIONS: This study demonstrates that CD34hi_ECs are markedly expanded in the aortic wall of TAK patients and enriched in angiogenesis-related processes. FGF2 is selectively overexpressed in vasa vasorum endothelial cells, accompanied by enhanced FGFR1, MAPK, and PI3K pathway gene expression in CD34hi_ECs, suggesting that the FGF2-FGFR1 axis may mediate pathological angiogenesis in TAK. Key Points • In TAK patients, a distinct subset of CD34hi_ECs endothelial cells was identified in aortic tissue, with biological processes predominantly enriched in angiogenesis-related pathways. • Serum and aortic tissue levels of FGF2 were significantly elevated in TAK patients compared to controls, with FGF2 primarily localized around the vasa vasorum in tissue samples. • FGFR1 and genes involved in the downstream MAPK/ERK and PI3K/AKT signaling pathways were upregulated in CD34hi_ECs.
PMID:42067750 | DOI:10.1007/s10067-026-08140-9