| First Author | Westmuckett AD | Year | 2009 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 29 |
| Issue | 11 | Pages | 1730-6 |
| PubMed ID | 19679829 | Mgi Jnum | J:167800 |
| Mgi Id | MGI:4880619 | Doi | 10.1161/ATVBAHA.109.192963 |
| Citation | Westmuckett AD, et al. (2009) Lack of tyrosylprotein sulfotransferase activity in hematopoietic cells drastically attenuates atherosclerosis in Ldlr-/- mice. Arterioscler Thromb Vasc Biol 29(11):1730-6 |
| abstractText | OBJECTIVE: Leukocyte recruitment is a major contributor in the development of atherosclerosis and requires a variety of proteins such as adhesion molecules, chemokines, and chemokine receptors. Several key molecular players implicated in this process are expressed on monocytes and require protein-tyrosine sulfation for optimal function in vitro, including human CCR2, CCR5, CX3CR1, and PSGL-1. We therefore hypothesized that protein-tyrosine sulfation in hematopoietic cells plays an important role in the development of atherosclerosis. METHODS AND RESULTS: Lethally-irradiated Ldlr(-/-) mice were rescued with hematopoietic progenitors lacking tyrosylprotein sulfotransferase (TPST) activity attributable to deletion of the Tpst1 and Tpst2 genes. TPST deficient progenitors efficiently reconstituted hematopoiesis in Ldlr(-/-) recipients and transplantation had no effect on plasma lipids on a standard or atherogenic diet. However, we observed a substantial reduction in the size of atherosclerotic lesions and the number of macrophages in lesions from hyperlipidemic Ldlr(-/-) recipients transplanted with TPST deficient progenitors compared to wild-type progenitors. We also document for the first time that murine Psgl-1 and Cx3cr1 are tyrosine-sulfated. CONCLUSIONS: These data demonstrate that protein-tyrosine sulfation is an important contributor to monocytes/macrophage recruitment and/or retention in a mouse model of atherosclerosis. |
