What question did this study set out to answer?

This research aims to explore the cellular and molecular changes associated with neointima formation in human saphenous veins used for coronary bypass.

January 24, 2026

Comprehensive transcriptomics and proteomics analysis of neointima formation in human saphenous vein: implications for bypass graft disease

Key Points

This research aims to explore the cellular and molecular changes associated with neointima formation in human saphenous veins used for coronary bypass.
Conducted transcriptomics and proteomics analysis in ex vivo cultured human saphenous veins.
Performed histological examination to observe elastin degradation and neointima characteristics.
Utilized RNA sequencing to analyze gene expression changes related to inflammation and cell proliferation.
Applied spatial transcriptomics to assess regional gene expression in veins from various patients.
Histological findings showed significant neointima formation and elastin degradation in cultured veins.
Sex and body mass index notably influenced the extent of neointima formation, particularly in males.
RNA sequencing indicated upregulation of pro-inflammatory genes and cellular stress markers during neointima formation.
Proteomic analysis found increases in extracellular matrix and coagulation proteins while metabolic proteins decreased.
Identified dynamic shifts in vascular smooth muscle cells and fibroblast states, including novel gene expressions during neointima development.

Abstract

Introduction: Human saphenous veins (SV) are widely used as grafts in coronary artery bypass (CABG) surgery but often fail due to neointima formation. Little is known, however, regarding the cellular, transcriptomic and proteomic dynamics of neointima formation in human veins. Here, we performed transcriptomics and proteomics analysis in an ex vivo tissue culture model of neointima formation in human SV procured for CABG surgery. Methods and results: Histological examination demonstrated significant elastin degradation and neointima formation (indicated by increased neointima area and neointima/media ratio) in SV subjected to tissue culture. Analysis of data from 72 patients suggest that the progression of SV remodeling and neointima formation differs according to sex and body mass index, which negatively associated with neointima formation in males only. RNA sequencing demonstrated upregulation of pro-inflammatory and proliferation-related genes during neointima formation and identified novel processes, including increased cellular stress and DNA damage responses, reflecting tissue trauma associated with vein harvesting. Proteomic analysis identified upregulated extracellular matrix-related and coagulation/thrombosis proteins and downregulated metabolic proteins. Spatial transcriptomics, used to infer regionally enriched gene expression, suggested dynamic alterations in fibroblast and vascular smooth muscle cell (VSMC) states during neointima formation. Specifically, we identified the emergence of HES1+ and MMP2+/MMP14+ expression in VSMCs and fibroblasts, respectively, during neointima formation. Furthermore, our data suggest that MIR647, identified through screening, maintains VSMC contractile gene expression. Conclusion Our findings suggest dynamic transcriptomic and proteomic changes during neointima formation in human veins and provide useful mechanistic information for the pathogenesis of SV graft disease.

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