title: Pravastatin and Sarpogrelate Synergistically Ameliorate Atherosclerosis in LDLr-Knockout Mice.
abstract: Pravastatin is a lipid-lowering agent that attenuates atherosclerosis. However, the multifactorial pathogenesis of atherosclerosis requires other drugs with different anti-atherogenic mechanisms. We chose sarpogrelate as an anti-platelet agent and a novel component of a complex drug with pravastatin due to its high potential but little information on its beneficial effects on atherosclerosis. Low-density lipoprotein receptor-knockout mice were fed a high-fat, high-cholesterol diet and treated with pravastatin alone, sarpogrelate alone, or a combination of both drugs. Although sarpogrelate alone did not significantly reduce atherosclerotic plaque areas, co-treatment with pravastatin significantly decreased aortic lesions compared to those of the pravastatin alone treated group. The combined therapy was markedly more effective than that of the single therapies in terms of foam cell formation, smooth muscle cell proliferation, and inflammatory cytokine levels. These results suggest that pravastatin and sarpogrelate combined therapy may provide a new therapeutic strategy for treating atherosclerosis.
authors.affiliation: Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon, Republic of Korea.
authors.forename: Kyung-Yeon
authors.initials: KY
authors.lastname: Park
authors.affiliation: Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon, Republic of Korea.
authors.forename: Euichaul
authors.initials: E
authors.lastname: Oh
authors.affiliation: Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon, Republic of Korea.
authors.forename: Mi-Kyoung
authors.initials: MK
authors.lastname: Kwak
authors.affiliation: Department of Biotechnology and Bioinformatics, College of Science and Technology, Korea University, Sejong, Republic of Korea.
authors.forename: Hyun Sik
authors.initials: HS
authors.lastname: Jun
authors.affiliation: Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon, Republic of Korea.
authors.forename: Tae-Hwe
authors.initials: TH
authors.lastname: Heo
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D055786:Gene Knockout Techniques; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000517:prevention & control; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics*; D013386:Succinates / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D000960:Hypolipidemic Agents; D008055:Lipids; D011973:Receptors, LDL; D013386:Succinates; D018799:Intercellular Adhesion Molecule-1; C064294:sarpogrelate; D017035:Pravastatin