title: Effect of α-linolenic acid-modified low molecular weight chondroitin sulfate on atherosclerosis in apoE-deficient mice.
abstract: 8-week-age male ApoE(-/-) mice were fed with the atherogenic diet together with or without tested compounds (rosuvastatin calcium, α-LNA-LMWCS, LMWCS and α-LNA) for 16 weeks. When the animals were killed, blood plasma was isolated to test the level of TC, LDL-C, TNF-α, IL-6 and CRP by biochemistry analysis and ELISA method. The whole aorta and aortic root sections were also collected to study atherogenesis level and reveal the possible mechanism by histological examination, real-time PCR and Western blot analysis.
  
  
  
  The level of TC, LDL-C, TNF-α, IL-6 and CRP in plasma in H-LNA-LMWCS group were significantly lower than those of the control group (rosuvastatin calcium). Plaques in H-LNA-LMWCS group showed higher content of smooth muscle cells, lower content of lipid and macrophages, and lower mRNA levels of TNF-α, IL-6, CRP, MCP-1, VCAM-1 and ICAM-1 than those in the control group. In addition, α-LNA-LMWCS could reduce the nuclear translocation of NF-κB, inhibit expressions of p-ERK1/2, p-p38, MCP-1, VCAM-1 and ICAM-1 in mice aorta.
  
  
  
  α-LNA-LMWCS exhibited anti-atherosclerosis effect through regulating the lipid metabolism and diminishing the synthesis of pro-inflammatory cytokines. The possible mechanism may be that α-LNA-LMWCS could influence MAPK/ NF-κB related signal pathway.
  
  
  
  The results may provide significant suggestions for the application of α-LNA-LMWCS in anti-atherosclerosis.
authors.affiliation: College of Pharmaceutical Sciences, Institute of Pharmaceutical Technology, Shandong Key Laboratory of Cerebral Microcirculation,Taishan Medical University, Taian 271000, Shandong, China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Pingli
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, China.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, China. Electronic address: 111925wj@163.com.
authors.forename: Fengshan
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics; D018932:Chemokine CCL2 / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008042:Linolenic Acids / Q000737:chemistry; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D008042:Linolenic Acids; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002809:Chondroitin Sulfates
keywords: NF-κB; anti-atherosclerosis; anti-inflammation; α-linolenic acid-modified low molecular weight chondroitin sulfate