A platelet-monocyte pyroptotic axis mediates uremic cardiomyopathy: critical role of PF4 and hematopoietic caspase-1.
Y, Y., M, Z., M, C., X, L., J, X., T, Z., D, Z., D, K., L, M., & A, P. (2026). A platelet-monocyte pyroptotic axis mediates uremic cardiomyopathy: critical role of PF4 and hematopoietic caspase-1.. Inflammation research : official journal of the European Histamine Research Society ... [et al.]. https://doi.org/10.1007/s00011-026-02311-9
Y Y, M Z, M C, X L, J X, T Z, et al. A platelet-monocyte pyroptotic axis mediates uremic cardiomyopathy: critical role of PF4 and hematopoietic caspase-1.. Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 2026; doi: 10.1007/s00011-026-02311-9
Y Y, M Z, M C, et al. A platelet-monocyte pyroptotic axis mediates uremic cardiomyopathy: critical role of PF4 and hematopoietic caspase-1.[J]. Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 2026. DOI: 10.1007/s00011-026-02311-9.
@article{y2026,
author = {Yang Y and Zhang M and Chen M and Li X and Xu J and Zhang T and Zhang D and Kong D and Ma L and Peng A},
title = {A platelet-monocyte pyroptotic axis mediates uremic cardiomyopathy: critical role of PF4 and hematopoietic caspase-1.},
journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]},
year = {2026},
doi = {10.1007/s00011-026-02311-9},
note = {PMID: 42406141},
}
TY - JOUR AU - Yang Y AU - Zhang M AU - Chen M AU - Li X AU - Xu J AU - Zhang T AU - Zhang D AU - Kong D AU - Ma L AU - Peng A TI - A platelet-monocyte pyroptotic axis mediates uremic cardiomyopathy: critical role of PF4 and hematopoietic caspase-1. T2 - Inflammation research : official journal of the European Histamine Research Society ... [et al.] PY - 2026 DO - 10.1007/s00011-026-02311-9 AN - PMID:42406141 ER -
BACKGROUND: Cardiovascular disease is the leading cause of death in end-stage renal disease (ESRD). While platelet activation and monocyte inflammation are hallmarks of uremia, how platelet-derived factors drive monocyte-mediated cardiac remodeling remains elusive. We investigated the role of platelet factor-4 (PF4) in monocyte pyroptosis and its contribution to uremic cardiomyopathy. METHODS: A uremic mouse model was established by 5/6 nephrectomy (Nx). Differentially expressed genes between Ly6C⁺ and Ly6C⁻ monocyte subsets were identified by microarray and WGCNA. PF4 effects were assessed by systemic administration with or without CXCR3 inhibition or PF4 neutralization. Caspase-1 activation was evaluated by FAM-FLICA staining and IL-1β ELISA. The role of caspase-1 was examined using global Casp1⁻/⁻ mice and bone marrow (BM) transfer experiments. RESULTS: In uremic mice, circulating Ly6C⁺ monocytes decreased time-dependently. Bioinformatics identified Pf4 as a key hub gene, with six pyroptosis-associated genes upregulated in Ly6C⁺ monocytes versus sham controls. PF4 infusion, at least in part through CXCR3, shortened Ly6C⁺ monocyte lifespan, upregulated pyroptosis-related genes, increased active caspase-1⁺ cells and IL-1β release, and accelerated cardiac dysfunction and fibrosis. CXCR3 inhibition or PF4 neutralization attenuated these effects. Global Casp1 knockout, which retained intact Casp11 expression, protected mice from PF4-exacerbated cardiac injury. BM transplantation from Casp1⁻/⁻ into wild-type mice conferred the same protective phenotype, identifying BM-derived caspase-1 as a key driver. CONCLUSION: Our study identifies a pathway where PF4, acting partly through CXCR3, contributes to caspase-1-dependent pyroptosis in Ly6C⁺ monocytes, driving pathological cardiac remodeling in uremia. Targeting this axis in BM-derived cells may represent a therapeutic strategy for heart failure in ESRD.