PloS one · 2013
Knockout of CD8 delays reendothelialization and accelerates neointima formation in injured arteries of mouse via TNF-α inhibiting the endothelial cells migration.
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Zhang Jun-Meng, Wang Ying, Miao Yan-Ju, Zhang Yi, Wu Yi-Na, Jia Li-Xin, Qi Yong-Fen, Du Jie
Аннотация
OBJECTIVE: Delayed 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 RESULTS: Immunofluorescence 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.
CONCLUSION: 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 TNF-α production promoting ECs migration.
METHODS AND RESULTS: Immunofluorescence 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.
CONCLUSION: 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 TNF-α production promoting ECs migration.