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Imaging · study · 2026

Single Cell and Spatial Transcriptomics Identify Novel Immune-Stromal Interactions in Cardiac Allograft Vasculopathy

Listed in NCBI GEO

Cardiac allograft vasculopathy (CAV) is the leading cause of mortality in heart transplant recipients.

Description

Despite the prevalence of CAV, there are no targeted therapeutic options to prevent or reverse disease progression, and patients ultimately require retransplant. CAV is characterized by progressive neointimal hyperplasia in donor heart coronary arteries, leading to luminal obliteration and ultimately allograft failure or sudden cardiac death.

Although immune and stromal cell interactions are believed to play a key role in CAV pathogenesis, the specific cellular players and molecular signals driving disease remain undefined. In this study, we leverage single-cell RNA sequencing and spatial transcriptomics of human coronary arteries to transcriptionally characterize CAV and define the neointimal microenvironment. We compare arteries with CAV to atherosclerotic coronary artery disease and non-disease controls to identify a unique CAV transcriptional signature.

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Integration of single-cell RNA sequencing and spatial transcriptomic datasets revealed that modulated vascular smooth muscle cells and macrophage subsets dominate the CAV neointima and suggest that these cells interact to propagate type 1 interferon (IFN)-mediated inflammation. In a mouse CAV model, we demonstrate that interferon blockade with Ruxolitinib significantly reduced the incidence of CAV and prolonged allograft survival.

Collectively, this study offers a novel and detailed characterization of the unique cellular and transcriptional landscape of CAV and identify a candidate pathway that may underly CAV pathogenesis, which could serve as a new therapeutic target for this devastating disease.

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Topics

Stated by source
Homo sapiens · Other
From keywords
Life Sciences
Inferred from text
Disease 75% · Heart 75% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 12 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE3163907 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[anatomy].local:anatomy:heartenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[disease].local:disease:diseaseenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:othersource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:single-cell-rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title