Effects of rosuvastatin on the coordinated proteomic response of human coronary smooth muscle cells to low density lipoproteins

Introduction: The clinical benefits of statins in reducing coronary events have been related to repopulation of the acellular core of atheromatous plaques with vascular smooth muscle cells (VSMC) and plaque stabilization. Intimal low-density lipoproteins (LDL) have been associated with VSMC phenotypic modulation and plaque destabilization. We have recently reported that LDL impair vascular remodelling because of changes affecting cytoskeleton proteins. Here, we used a proteomic approach to study whether rosuvastatin reverses the effects induced by atherogenic concentrations of LDL in human VSMC.Methods and Results: VSMC treated with/without 10 mu M rosuvastatin were incubated in the presence/absence of 100 mu g/mL LDL for 24 h. Using 2DE and MALDI-ToF MS, we identified 39 non-redundant proteins (52 spots) with differential expression in LDL-treated cells. Thirteen of these proteins were reverted to normal levels by rosuvastatin. Thus, four proteins showed decreased intensity, six showed increased intensity, and three multispot proteins changed their distribution pattern in the rosuvastatin group. These proteins were identified as components of endoplasmic reticulum, mitochondrion, nucleus, cell membrane, cytoskeleton, and cytoplasm. In LDL-VSMC, rosuvastatin affected proteins involved in a variety of functions including cytoskeleton dynamics, chaperone activity, carbohydrate metabolism, protein biosynthesis and folding, kinase activity, redox processes, cytoprotective effects, and cell proliferation.Conclusions: Our results demonstrate that the reversing effects of rosuvastatin in LDL-enriched VSMC affect functional proteins with a role in cellular metabolism and dynamics, which might contribute to the beneficial effects of statins by stabilizing lipid-rich atherosclerotic plaques in human atherosclerosis. (C) 2011 Elsevier Espana, S.L. and SEA. All rights reserved.