title: The combination of L-4F and simvastatin stimulate cholesterol efflux and related proteins expressions to reduce atherosclerotic lesions in apoE knockout mice.
abstract: BACKGROUND
  Both L-4F, one apolipoprotein A-1 mimetic peptide, and statins can reduce progression of atherosclerosis by different mechanisms. The combination of the two drugs can cause lesion regression by rendering HDL anti-inflammatory. We postulated that combination of L-4F and simvastatin may stimulate cholesterol efflux and related proteins expressions to alleviate atherosclerosis.
  
  
  METHODS
  Thirty male wild-type (W-T) C57 BL/6 mice and apo E(-/-) mice were divided into five groups: W-T group, atherosclerosis (AS) group, simvastatin group, L-4F group and the combination of simvastatin and L-4F group. After 16 weeks, serum lipids, atherosclerotic lesion areas, cholesterol efflux and the expressions of related proteins including ABCA1, SR-BI, ABCG1, LXRα and PPARγ were evaluated.
  
  
  RESULTS
  The aortic atherosclerotic lesion areas were reduced more significantly by combination of both drugs than single agent, and cholesterol efflux was promoted more in combination group than simvastatin and L-4F group. Besides, the combination group promoted expressions of cholesterol efflux related proteins.
  
  
  CONCLUSIONS
  The combination of L-4F and simvastatin reduced atherosclerotic lesions, which stimulates cholesterol efflux by promoting the expressions of related proteins. In addition, these results help us further understand that the regression of the atherosclerosis would be assessed by reduction in LDL-C with increase of cholesterol efflux.
authors: Ru
authors: R
authors: Ying
authors: Department of Cardiology, Zhongshan hospital, Sun Yat- Sen University, Zhongshan, Guang Dong, China. yuanyong66688@163.com.
authors: Yong
authors: Y
authors: Yuan
authors: Ya-Fei
authors: YF
authors: Qin
authors: Di
authors: D
authors: Tian
authors: Li
authors: L
authors: Feng
authors: Zhi-Gang
authors: ZG
authors: Guo
authors: Yan-Xiang
authors: YX
authors: Sun
authors: Ming-Xing
authors: MX
authors: Li
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood; D004359:Drug Therapy, Combination; D015870:Gene Expression / Q000187:drug effects*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018716:Molecular Mimicry; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D002784:Cholesterol; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D010455:Peptides; D051122:Scavenger Receptors, Class B; D019821:Simvastatin; C577833:Abca1 protein, mouse; C487540:ABCG1 protein, mouse; C472885:L-4F peptide; C000605214:Nr1h3 protein, mouse; C454739:Scarb1 protein, mouse