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Journal of Lipid Research, Vol. 50, 1832-1841, September 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Effects of rosuvastatin on electronegative LDL as characterized by capillary isotachophoresis: the ROSARY Study

Bo Zhang^*, Akira Matsunaga^*, David L. Rainwater, Shin-ichiro Miura^*, Keita Noda^*, Hiroaki Nishikawa^*, Yoshinari Uehara^*, Kazuyuki Shirai^*, Masahiro Ogawa^* and Keijiro Saku^1,*

^* Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549

¹ To whom correspondence should be addressed. e-mail: saku-k{at}fukuoka-u.ac.jp

Electronegative LDL, a charge-modified LDL (cm-LDL) subfraction that is more negatively charged than normal LDL, has been shown to be inflammatory. 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-modified 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 [slow-migrating 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.

Supplementary key words LDL particle concentrations • hypercholesterolemia • small dense LDL • statins

Abbreviations: apo, apolipoprotein; cITP, capillary isotachophoresis; cm-LDL, charge-modified LDL; CHD, coronary heart disease; CRP, C-reactive protein; DM, diabetes mellitus; FC, free cholesterol; fHDL, fast-migrating HDL; fLDL, fast-migrating LDL; fTRL, fast-migrating TRL; HC, hypercholesterolemia; HDL-C, HDL cholesterol; HDL-PAF-AH, HDL-associated PAF-AH; HT, hypertension; HTG, hypertriglyceridemia; iHDL, intermediate-migrating HDL; LDL(-), electronegative LDL; LDL-C, LDL cholesterol; LDL-PAF-AH, LDL-associated PAF-AH; NL, normolipidemic; OxLDL, oxidized LDL; PAF-AH, platelet-activating factor acetylhydrolase; PL, phospholipids; RLP-C, remnant-like particle cholesterol; sLDL, slow-migrating LDL; sdLDL, small, dense LDL; sd-cm-LDL, small, dense charge-modified LDL; sd-sLDL, small, dense, slow-migrating LDL; sHDL, slow-migrating HDL; sTRL, slow-migrating TRL; TG, triglyceride; TRL, TG-rich lipoprotein; vfLDL, very-fast-migrating LDL

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