Inhibition of aortic CX3CR1+ macrophages mitigates thoracic aortic aneurysm progression in Marfan syndrome in mice.

ABSTRACT: The pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is generally attributed to vascular smooth muscle cell (VSMC) pathologies. However, the role of immune cell-mediated inflammation remains elusive. Single-cell RNA sequencing identified a subset of CX3CR1+ macrophages mainly located in the intima in the aortic roots and ascending aortas of Fbn1C1041G/+ mice, further validated in MFS patients. Specific elimination of CX3CR1+ cells by diphtheria toxin in Cx3cr1-CreERT2iDTRF/+Fbn1C1041G/+ mice efficiently ameliorated TAA progression. Administering the monoclonal antibodies to respectively neutralize TNF-α and IGF1 produced by CX3CR1+ cells from MFS patients greatly suppressed the cocultured MFS patient-specific induced pluripotent stem cell-derived VSMC inflammation. B

SUBMITTER: Huang J 

PROVIDER: S-EPMC11735105 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature