An increased low-density lipoprotein cholesterol (LDL-C) level is an established risk factor for cardiovascular disease. Statins (3-hydroxy-3-methylglutaryl CoA reductase inhibi-

This article is available online at http://www.jlr.org An increased low-density lipoprotein cholesterol (LDL-C) level is an established risk factor for cardiovascular disease. Statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) effectively reduce LDL-C levels and the risk of cardiovascular events ( 1 ). Statins also diminish infl ammation as indicated by a reduction of C-reactive protein (CRP) ( 2, 3 ). However, the mechanism by which statins exert their antiinfl ammatory action is not fully understood. Modifi ed forms of LDL that exist in human plasma, including oxidized LDL (OxLDL), small, dense LDL (sdLDL), and glycated LDL, are considered to be atherogenic. Increased OxLDL and sdLDL levels are associated with an increased risk of coronary heart disease (CHD) ( 4, 5 ). Various forms of modifi ed LDL share a common characteristic in that they show increased electrophoretic mobility compared with normal LDL. An LDL subfraction that is more negatively charged than normal LDL has been separated by anion-exchange chromatography and is defi ned as electronegative LDL [LDL(-)] ( 6 ). The proportion of LDL(-) in total LDL has been shown to be increased in patients with hypercholesterolemia (HC), hypertriglyceridemia (HTG), diabetes mellitus (DM), and CHD ( 7–10 ). LDL(-) separated from either normal subjects or patients with HC has been consistently shown to be infl ammatory Abstract Electronegative LDL, a charge-modifi ed LDL (cm-LDL) subfraction that is more negatively charged than normal LDL, has been shown to be infl ammatory. We previously showed that pravastatin and simvastatin reduced the electronegative LDL subfraction, fast-migrating LDL (fLDL), as analyzed by capillary isotachophoresis (cITP). The present study examined the effects of rosuvastatin on the more electronegative LDL subfraction, very-fast-migrating LDL (vfLDL), and small, dense charge-modifi ed LDL (sd-cm-LDL) subfractions. Patients with hypercholesterolemia or those who were being treated with statins (n = 81) were treated with or switched to 2.5 mg/d rosuvastatin for 3 months. Rosuvastatin treatment effectively reduced cITP cm-LDL subfractions of LDL (vfLDL and fLDL) or sdLDL (sd-vfLDL and sd-fLDL), which were closely related to each other but were different from the normal subfraction of LDL [slowmigrating LDL (sLDL)] or sdLDL (sd-sLDL) in their relation to the levels of remnant-like particle cholesterol (RLP-C), apolipoprotein (apo) C-II, and apoE. The percent changes in cm-LDL or sd-cm-LDL caused by rosuvastatin were correlated with those in the particle concentrations of LDL or sdLDL measured as LDL-apoB or sdLDL-apoB and the levels of HDL-C, RLP-C, apoC-II, and apoE. In conclusion, rosuvastatin effectively reduced both the vfLDL subfraction and sd-cm-LDL subfractions as analyzed by cITP. — Zhang, B., A. Matsunaga, D. L. Rainwater, S-i. Miura, K. Noda, H. Nishikawa, Y. Uehara, K. Shirai, M. Ogawa, and K. Saku. Effects of rosuvastatin on electronegative LDL as characterized by capillary isotachophoresis: the ROSARY Study. J. Lipid Res. 2009. 50: 1832–1841.