| First Author | Becker L | Year | 2010 |
| Journal | Cell Metab | Volume | 11 |
| Issue | 2 | Pages | 125-35 |
| PubMed ID | 20142100 | Mgi Jnum | J:158623 |
| Mgi Id | MGI:4439240 | Doi | 10.1016/j.cmet.2010.01.003 |
| Citation | Becker L, et al. (2010) A macrophage sterol-responsive network linked to atherogenesis. Cell Metab 11(2):125-35 |
| abstractText | Cholesteryl ester accumulation by macrophages is a critical early event in atherogenesis. To test the hypothesis that sterol loading promotes foam cell formation and vascular disease by perturbing a network of interacting proteins, we used a global approach to identify proteins that are differentially expressed when macrophages are loaded with cholesterol in vivo. Our analysis revealed a sterol-responsive network that is highly enriched in proteins with known physical interactions, established roles in vesicular transport, and demonstrated atherosclerotic phenotypes in mice. Pharmacologic intervention with a statin or rosiglitazone and use of mice deficient in LDL receptor or apolipoprotein E implicated the network in atherosclerosis. Biochemical fractionation revealed that most of the sterol-responsive proteins resided in microvesicles, providing a physical basis for the network's functional and biochemical properties. These observations identify a highly integrated network of proteins whose expression is influenced by environmental, genetic, and pharmacological factors implicated in atherogenesis. |
