Danshensu protects vascular endothelia in a rat model of hyperhomocysteinemia.
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.
Yang
Rui-xue
RX
Chinese Ministry of Education, Shandong University, Ji-nan, China.
Huang
Shan-ying
SY
Yan
Fang-fang
FF
Lu
Xiao-ting
XT
Xing
Yi-fan
YF
Liu
Yan
Y
Liu
Yun-fang
YF
Zhao
Yu-xia
YX
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
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