TY - JOUR
T1 - Ticlopidine attenuates progression of atherosclerosis in apolipoprotein E and low density lipoprotein receptor double knockout mice
AU - Jawien, Jacek
AU - Csanyi, Gabor
AU - Gajda, Mariusz
AU - Mateuszuk, Lukasz
AU - Lomnicka, Magdalena
AU - Korbut, Ryszard
AU - Chlopicki, Stefan
N1 - Funding Information:
This article was supported by a grant from the Polish Ministry of Science and Information Society Technologies (MNiI) nr 2 P05A 084 26 for 2004–2006 (J.J.) and by grants No P05A 003 25 and PBZ-KBN-101/T09/2003/6 (S.C.). Professor Stefan Chlopicki is the recipient of a Professorial grant from the Foundation for Polish Science (SP/04/04). The authors thank Pawel Krzeczunowicz for proof-reading of the manuscript.
PY - 2007/2/5
Y1 - 2007/2/5
N2 - Platelets are involved in the development of atherothrombosis. However, the anti-atherosclerotic effects of thienopiridines have not been, as yet, proven. We analyzed the effects of ticlopidine on atherogenesis in apolipoprotein E/low density lipoprotein receptor double knockout (apoE/LDLR-/-) mice. 2-month-old apoE/LDLR-/- mice fed a Western diet (21% fat, 0.15% cholesterol) were treated with ticlopidine (90 mg/kg/day) for a period of 4 months. In 6-month-old apoE/LDLR-/- mice treated with ticlopidine and in their non-treated counterparts we analyzed: cholesterol and triglyceride levels, the size of atherosclerotic plaques in aortic roots (oil red-O staining, cross-section method), and in the whole aorta (Sudan IV staining, en face method), the number of macrophages in atherosclerotic plaque (CD68 staining), as well as the endothelial function in the isolated thoracic aorta. Concentrations of total cholesterol and triglycerides in plasma were not altered by treatment with ticlopidine. However, the size of atherosclerotic plaques measured in aortic roots by the cross-section method and the number of macrophages estimated by anti-CD68 staining were significantly reduced by ticlopidine treatment. In contrast, the effect of ticlopidine on the area covered by plaques in the whole aorta (en face analysis) was not statistically significant. Importantly, acetylcholine-induced vasodilation in isolated aorta was improved in ticlopidine-treated apoE/LDLR-/- mice as compared to their non-treated counterparts. In conclusion, ticlopidine attenuates the progression of atherosclerosis and improves the endothelial function in apoE/LDLR-/- mice.
AB - Platelets are involved in the development of atherothrombosis. However, the anti-atherosclerotic effects of thienopiridines have not been, as yet, proven. We analyzed the effects of ticlopidine on atherogenesis in apolipoprotein E/low density lipoprotein receptor double knockout (apoE/LDLR-/-) mice. 2-month-old apoE/LDLR-/- mice fed a Western diet (21% fat, 0.15% cholesterol) were treated with ticlopidine (90 mg/kg/day) for a period of 4 months. In 6-month-old apoE/LDLR-/- mice treated with ticlopidine and in their non-treated counterparts we analyzed: cholesterol and triglyceride levels, the size of atherosclerotic plaques in aortic roots (oil red-O staining, cross-section method), and in the whole aorta (Sudan IV staining, en face method), the number of macrophages in atherosclerotic plaque (CD68 staining), as well as the endothelial function in the isolated thoracic aorta. Concentrations of total cholesterol and triglycerides in plasma were not altered by treatment with ticlopidine. However, the size of atherosclerotic plaques measured in aortic roots by the cross-section method and the number of macrophages estimated by anti-CD68 staining were significantly reduced by ticlopidine treatment. In contrast, the effect of ticlopidine on the area covered by plaques in the whole aorta (en face analysis) was not statistically significant. Importantly, acetylcholine-induced vasodilation in isolated aorta was improved in ticlopidine-treated apoE/LDLR-/- mice as compared to their non-treated counterparts. In conclusion, ticlopidine attenuates the progression of atherosclerosis and improves the endothelial function in apoE/LDLR-/- mice.
KW - ApoE/LDLR mice
KW - Atherosclerosis
KW - Endothelium
KW - Ticlopidine
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U2 - 10.1016/j.ejphar.2006.11.028
DO - 10.1016/j.ejphar.2006.11.028
M3 - Article
C2 - 17174298
AN - SCOPUS:33846117498
SN - 0014-2999
VL - 556
SP - 129
EP - 135
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -