Pravastatin and Sarpogrelate Synergistically Ameliorate Atherosclerosis in LDLr-Knockout Mice

• Published in: PloS one 2016-03, Vol.11 (3), p.e0150791-e0150791
• Main Authors: Park, Kyung-Yeon, Oh, Euichaul, Kwak, Mi-Kyoung, Jun, Hyun Sik, Heo, Tae-Hwe
• Format: Article
• Language: English
• Subjects: Animals; Aorta; Arteriosclerosis; Atherosclerosis; Atherosclerosis - blood; Atherosclerosis - drug therapy; Atherosclerosis - genetics; Atherosclerosis - immunology; Biology and Life Sciences; Blood platelets; Cardiovascular disease; Cell proliferation; Cell Proliferation - drug effects; Cholesterol; Comparative analysis; Complications and side effects; Coronary vessels; Cytokines - metabolism; Diabetes; Diet; Dosage and administration; Drug Synergism; Drug therapy; Drugs; Foam; Foams; Gene Expression Regulation - drug effects; Gene Knockout Techniques; Genetic aspects; Heart attacks; Histology; Hypolipidemic Agents - pharmacology; Hypolipidemic Agents - therapeutic use; Inflammation; Intercellular Adhesion Molecule-1 - metabolism; Laboratory animals; Lesions; Lipids - blood; Lipoprotein (low density) receptors; Low density lipoprotein receptors; Low density lipoproteins; Macrophages - drug effects; Macrophages - immunology; Male; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes - drug effects; Monocytes - immunology; Muscles; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - pathology; Pathogenesis; Pharmaceutical sciences; Pharmacy; Physiological aspects; Plaque, Atherosclerotic - prevention & control; Pravastatin; Pravastatin - pharmacology; Pravastatin - therapeutic use; Rabbits; Receptor density; Receptors, LDL - deficiency; Receptors, LDL - genetics; Rodents; Signal transduction; Smooth muscle; Statins; Studies; Succinates - pharmacology; Succinates - therapeutic use; Therapy; Thrombosis; Transgenic animals
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0150791

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.