Conferenze
Macrophage protein interaction networks and atherosclerosis: combining proteomics and bioinformatics
17 settembre 2008
Department of Pharmacological Sciences, University of Milan
Lev Becker
Macrophages that accumulate cholesteryl ester become foam cells, which promote atherogenesis. To investigate the pathways responsible for this transition, we used mass spectrometry to probe the shed and secreted proteome of macrophages and foam cells. In the macrophage proteome, we identified a network of highly connected proteins that comprised 10 functional modules. Sterol loading of macrophages in vitro and in vivo coordinately regulated protein expression of a subnetwork enriched in 3 of the modules. One known module centered on lipid metabolism.
Unexpectedly, the other two were enriched in proteins implicated in lysosomal biology and complement regulation. Treating hypercholesterolemic mice with simvastatin attenuated the altered pattern of subnetwork protein expression without altering plasma cholesterol levels. Importantly, more than one-third of the subnetwork proteins associated with atherosclerosis phenotypes in genetically engineered mice. These observations suggest that interactions among the complement, lipid metabolism, and lysosomal systems are central to foam cell formation and atherogenesis.
