Abstract
ObjectiveDelayed or impaired reendothelialization is a major cause of stent thrombosis in the interventional treatment of coronary heart disease. T cells are involved in neointima formation of injured arteries. However, the regulated mechanism of reendothelialization and the role of CD8 T cell in reendothelialization are unclear.Methods and ResultsImmunofluorescence staining showed that CD8 positive cells were increased in wire injured femoral artery of mice. On day 21 after injury, elastin staining showed that knockout of CD8 (CD8−/−) significantly increased intimal thickness and a ratio of intima to media by 1.8 folds and 1.9 folds respectively in injured arteries. Evans blue staining showed that knockout of CD8 delayed the reendothelialization area on day 7 after injury (18.8±0.5% versus 42.1±5.6%, p<0.05). In vitro, a migration assay revealed that CD8−/− T cells co-cultured with WT macrophages significantly inhibited the migration of the endothelial cells (ECs); compared to CD4+ T cells, and CD8+ T cells could promote the ECs migration. Furthermore, real-time PCR analysis showed that knockout of CD8 increased the level of tumor necrosis factor α (TNF-α) in injured arteries and cytometric bead cytokine array showed that TNF-α was elevated in cultured CD8−/− T cells. Finally, a wound-healing assay showed that recombinant TNF-α significantly inhibited the migration of ECs.ConclusionOur study suggested that CD8+ T cells could promote the reendothelialization and inhibit the neointima formation after the artery wire injury, and this effect is at least partly dependent on decreasing TNF-α production promoting ECs migration.
Highlights
Drug-eluting stents (DES) are widely used in the interventional treatment of coronary heart diseases
Our study suggested that CD8+ T cells could promote the reendothelialization and inhibit the neointima formation after the artery wire injury, and this effect is at least partly dependent on decreasing tumor necrosis factor a (TNF-a) production promoting endothelial cells (ECs) migration
DES use has improved clinical outcome and has dramatically decreased the rates of restenosis than bare-metal stents (BMS)[1] after percutaneous coronary interventions (PCI), the significantly frequent instent thrombosis after implanting DES can lead to incidence of fatal myocardial infarction (MI) between 25 and 65% and nonMI-related fatality of 45–75%[2]
Summary
Drug-eluting stents (DES) are widely used in the interventional treatment of coronary heart diseases. The major cause of this treatment failure depends on the intrinsic nature of antiproliferative, anti-inflammatory and anti-migratory drugs, which impedes vessel healing and leads to incomplete reendothelialization and stent strut coverage [3,4,5]. Recent clinical studies have shown the potential value of strategies which targeted to increase endothelial progenitor cells capture and reendothelialization after PCI [10]. Previous studies showed that delayed healing of endothelial cells could lead to increased vascular inflammation, which further contributed to the neointima formation of injured arteries [11,12,13]. Whether the inflammatory cells recruited in the injured arteries affect the reendothelialization is not fully understood
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