| First Author | Lipinski MJ | Year | 2012 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 32 |
| Issue | 12 | Pages | 2855-61 |
| PubMed ID | 23042815 | Mgi Jnum | J:208316 |
| Mgi Id | MGI:5562636 | Doi | 10.1161/ATVBAHA.112.300352 |
| Citation | Lipinski MJ, et al. (2012) Loss of Id3 increases VCAM-1 expression, macrophage accumulation, and atherogenesis in Ldlr-/- mice. Arterioscler Thromb Vasc Biol 32(12):2855-61 |
| abstractText | OBJECTIVE: Inhibitor of differention-3 (Id3) promotes B cells homing to the aorta and atheroprotection in Apoe(-/-) mice. We sought to determine the impact of loss of Id3 in the Ldlr((-/-)) mouse model of diet-induced atherosclerosis and identify novel Id3 targets in the vessel wall. METHODS AND RESULTS: Ex vivo optical imaging confirmed that Id3((-/-)) Ldlr((-/-)) mice have significantly fewer aortic B cells than Id3((+/+)) Ldlr(-/-) mice. After 8 and 16 weeks of Western diet, Id3((-/-)) Ldlr((-/-)) mice developed significantly more atherosclerosis than Id3((+/+)) Ldlr((-/-)) mice, with Id3(+/-) Ldlr(-/-) mice demonstrating an intermediate phenotype. There were no differences in serum lipid levels between genotypes. Immunostaining demonstrated that aortas from Id3((-/-)) Ldlr((-/-)) mice had greater intimal macrophage density and C-C chemokine ligand 20 and vascular cell adhesion molecule 1 (VCAM-1) expression compared with Id3((+/+)) Ldlr(-/-) mice. Real-time polymerase chain reaction demonstrated increased VCAM-1 mRNA levels in the aortas of Id3(-/-) Ldlr(-/-) mice. Primary vascular smooth muscle cells from Id3((-/-)) mice expressed greater amounts of VCAM-1 protein compared with control. Gain and loss of function studies in primary vascular smooth muscle cells identified a role for Id3 in repressing VCAM-1 promoter activation. Chromatin immunoprecipitation demonstrated interaction of E12 with the VCAM-1 promoter, which is inhibited by Id3. CONCLUSIONS: Id3 is an atheroprotective transcription regulator with targets in both B cells and vessel wall cells leading to reduced macrophage accumulation and reduced atherosclerosis formation. |
