title: Danshensu protects vascular endothelia in a rat model of hyperhomocysteinemia.
abstract: OBJECTIVE
  To examine whether danshensu could protect vascular endothelia in a rat model of hyperhomocysteinemia.
  
  
  METHODS
  The model was established by feeding rats with a methionine-rich diet (1 g·kg⁻¹·d⁻¹) for 3 months. Immediately following the discontinuation of methionine-rich diet, rats were treated with danshensu (67.5 mg·kg⁻¹·d⁻¹, po) or saline for 3 additional months. One group of rats receiving vitamin mixture (folic acid, vitamin B12 and vitamin B6) was included as a positive control. One group of rats not exposed to methionine-rich diet was also included as a blank control. The expression of tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) protein in the descending aorta was examined using immunohistochemistry and Western blot. Homocysteine and blood concentration of endothelin and nitric oxide (NO) was also examined.
  
  
  RESULTS
  Methionine-rich diet resulted in accumulation of "foam cells", up-regulated expression of TNF-alpha and ICAM-1 in the descending aorta, and significantly increased serum homocysteine. Plasma endothelin concentration was significantly increased; NO was decreased. Danshensu treatment, either simultaneous to methionine-rich diet or afterwards, attenuated the above mentioned changes.
  
  
  CONCLUSIONS
  Chronic treatment with danshensu could prevent/attenuate the formation of atherosclerosis. Potential mechanisms include inhibited expression of representative proinflammatory cytokines and adhesion molecules in arterial endothelia. Changes in homocysteine and circulating molecules that control vascular contraction/relaxation via endothelial cells (eg, endothelin and NO) were also implicated.
authors.affiliation: Chinese Ministry of Education, Shandong University, Ji-nan, China.
authors.forename: Rui-xue
authors.initials: RX
authors.lastname: Yang
authors.forename: Shan-ying
authors.initials: SY
authors.lastname: Huang
authors.forename: Fang-fang
authors.initials: FF
authors.lastname: Yan
authors.forename: Xiao-ting
authors.initials: XT
authors.lastname: Lu
authors.forename: Yi-fan
authors.initials: YF
authors.lastname: Xing
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yun-fang
authors.initials: YF
authors.lastname: Liu
authors.forename: Yu-xia
authors.initials: YX
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000517:prevention & control; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004032:Diet; D004195:Disease Models, Animal; D016232:Endothelins / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007773:Lactates / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008715:Methionine; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002317:Cardiovascular Agents; D016232:Endothelins; D007773:Lactates; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; C035055:3,4-dihydroxyphenyllactic acid; D008715:Methionine