| First Author | Schiller NK | Year | 2002 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 22 |
| Issue | 8 | Pages | 1341-6 |
| PubMed ID | 12171798 | Mgi Jnum | J:103214 |
| Mgi Id | MGI:3608740 | Doi | 10.1161/01.atv.0000024082.46387.38 |
| Citation | Schiller NK, et al. (2002) Inflammation in atherosclerosis: lesion formation in LDL receptor-deficient mice with perforin and Lyst(beige) mutations. Arterioscler Thromb Vasc Biol 22(8):1341-6 |
| abstractText | OBJECTIVE: Natural killer (NK) cells have been identified in human vascular pathologies. In this study, we identified NK cells in aortic root atherosclerotic lesions of low density lipoprotein (LDL) receptor-deficient (LDLr-/-) mice. To characterize the role of NK cell-mediated cytolysis in atherosclerosis, we generated C57Bl/6 double-mutant mice by crossing LDLr-/- mice with NK cell-defective Lyst(beige) mice (creating beige,LDLr-/- mice) and with perforin-deficient mice (creating Pfp-/-,LDLr-/- mice). METHODS AND RESULTS: Male mice (8 to 10 weeks old) were fed a high-fat diet to induce atherosclerosis. Compared with LDLr-/- mice, beige,LDLr-/- mice had impaired NK cell cytolytic activity and significantly increased atherosclerosis (P<0.05). Pfp-/-,LDLr-/- mice had impaired NK cell cytolytic activity, yet they had lesions that were similar to those of control mice. This suggested that NK cell cytolysis did not play a significant role in atherosclerosis and that the exacerbated atherosclerosis of the beige,LDLr-/- mouse was independent of impaired NK cell cytolytic activity. Therefore, we investigated the role of T and B lymphocytes in atherosclerosis of beige mice by crossing them with recombinase activator gene 1-deficient LDLr-/- mice (Rag1-/-,LDLr-/- mice), thus creating beige,Rag1-/-, LDLr-/- mice. As in the double-mutant study, beige,Rag1-/-,LDLr-/- mice had significantly increased lesions compared with Rag1-/-,LDLr-/- control mice. CONCLUSIONS: Therefore, the Lyst(beige) mutation in LDLr-/- mice has proatherogenic properties that are independent of NK cell-mediated cytolysis and lymphocyte-mediated acquired immunity. |
