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Both apolipoprotein E and immune deficiency exacerbate neointimal hyperplasia after vascular injury in mice.

Abstract
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.
AuthorsBinghua Zhu, Catherine A Reardon, Godfrey S Getz, David Y Hui
JournalArteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 22 Issue 3 Pg. 450-5 (Mar 01 2002) ISSN: 1524-4636 [Electronic] United States
PMID11884289 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Apolipoproteins E
  • DNA-Binding Proteins
  • Rag2 protein, mouse
  • V(D)J recombination activating protein 2
Topics
  • Animals
  • Apolipoproteins E (genetics, physiology)
  • Carotid Stenosis (etiology, immunology, pathology)
  • Catheterization (adverse effects)
  • Cell Movement
  • DNA-Binding Proteins (genetics)
  • Graft Occlusion, Vascular (etiology, immunology, pathology)
  • Hyperplasia (etiology, immunology, pathology)
  • Lymphocytes (immunology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular (pathology)
  • Tunica Intima (pathology)

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