In this study, we investigated the role of T and B lymphocytes in neointimal
hyperplasia after endothelial denudation.
Catheter-induced endothelial denudation of wild-type mice resulted in rapid infiltration of lymphocytes to the site of injury. Mice defective in recombination-activating gene 2 (RAG2(-/-)) showed increased neointimal formation 14 days after
vascular injury in comparison to their wild-type immune-competent littermates. Immunohistochemical studies revealed the preponderance of smooth muscle cells and a significantly higher number of proliferating cells in the
neointima of the RAG2(-/-) mice. The
neointima size and the number of proliferating smooth muscle cells in the injured vessel of RAG2(-/-) mice were similar to those observed in the injured arteries of
apolipoprotein E (
apoE)-deficient (
apoE(-/-)) mice. Interestingly, mice with double
apoE and RAG2 gene mutations (
apoE(-/-) RAG2(-/-)) displayed similar neointimal characteristics as mice with a
single gene defect, suggesting a similar mechanism for
apoE and lymphocyte protection against injury-induced neointimal formation. The protective role of lymphocytes against neointimal formation after
vascular injury directly contrasts to their reported role in the promotion of
atherosclerosis, which was observed in both
apoE(+/+) and
apoE(-/-) mice. Thus, these results support the hypothesis of different etiology between
hyperlipidemia-induced
atherosclerosis and injury-induced vascular occlusion.