Abstract
Aim:
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.
Conclusion:
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.
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Acknowledgements
This study was supported by the National Basic Research Program of China (national “973” Project, 2005CB523301) and grants from the National Natural Science Foundation of China (No. 30801503, 30772810, 30873325). Assistance was provided by the key laboratory of cardiovascular remodeling and function research and the Chinese Ministry of Education.
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Yang, Rx., Huang, Sy., Yan, Ff. et al. Danshensu protects vascular endothelia in a rat model of hyperhomocysteinemia. Acta Pharmacol Sin 31, 1395–1400 (2010). https://doi.org/10.1038/aps.2010.167
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DOI: https://doi.org/10.1038/aps.2010.167
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