Abstract
Aim:
To investigate whether the combination of fluvastatin and losartan synergistically relieve atherosclerosis and plaque inflammation induced by a high-cholesterol diet in rabbits.
Methods:
Atherosclerosis was induced with a high-cholesterol diet for 3 months in 36 New Zealand white rabbits. The animals were randomly divided into model group, fluvastatin (10 mg·kg-1·d-1) group, losartan (25 mg·kg-1·d-1) group, and fluvastatin plus losartan group. After the 16-week treatments, the blood samples the animals were collected, and the thoracic aortas were examined immunohistochemically. The mRNA and protein expression levels of monocyte chemotactic protein-1 (MCP-1) were measured using RT-PCR and Western blot.
Results:
Compared to the treatment with losartan or fluvastatin alone, the combined treatment did not produce higher efficacy in reduction of blood cholesterol level. However, the combination did synergistically decrease the intimal and media thickness of thoracic aortas with significantly reduced macrophage infiltration and MCP-1 expression in the plaques.
Conclusion:
The combined treatment with losartan and fluvastatin significantly inhibited atherosclerotic progress and reduced inflammation associated with atherosclerotic plaques.
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Acknowledgements
This work was supported by National Natural Science Foundation of China (No 81170207) and the Program of Introducing Talents of Discipline to Universities (No B07035) and Shandong Natural Science Foundation of China (Nos 03BS37 and Y2006C68). We thank Rong WANG, Yong-huan ZHANG, and Xu-ping WANG for their technical assistance.
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Yang, Yp., Dong, Ql., Zhang, Xh. et al. Combination of fluvastatin and losartan relieves atherosclerosis and macrophage infiltration in atherosclerotic plaques in rabbits. Acta Pharmacol Sin 32, 1259–1265 (2011). https://doi.org/10.1038/aps.2011.95
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DOI: https://doi.org/10.1038/aps.2011.95
