Endothelial dysfunction precedes atherosclerotic lesions and platelet activation in high fat diet-induced prothrombotic state.
BACKGROUND
Earlier we have demonstrated a prothrombotic state in spontaneously atherogenic rodents kept on Western-style high fat diet. The aim of the present study was to investigate the cellular mechanism of such prothrombotic state.


METHODS
Two kinds of diets, Western-style high fat diet containing 20% fat (w/w) and 0.05% cholesterol (w/w) and low fat diet containing 7% fat without cholesterol based on AIN93G, were added to diet-sensitive apolipoprotein E and low-density lipoprotein receptor double deficient male mice for 12 or 18 weeks from 6 weeks of age. Atherosclerosis was assessed by morphometry of the aortic wall or lipid-stained lesions. Endothelial function was measured by flow-mediated vasodilation (FMV) of the femoral artery. Platelet reactivity was measured ex vivo by a shear-induced platelet aggregation test.


CONCLUSIONS
12 weeks feeding of mice with high fat diet significantly impaired FMV, as compared with mice fed with low fat diet (P<0.05). In contrast, there was no significant difference in the lipid-stained areas and in the reactivity of platelets between the two groups. 18 weeks feeding with high fat diet significantly impaired FMV (P<0.05) and enhanced both lipid-stained areas (P<0.05) and platelet reactivity (P<0.01). These findings show that in high fat diet-induced prothrombotic state, endothelial dysfunction precedes both the morphologically detectable lesions and the enhancement of platelet reactivity.
Aoki
Rumiko
R
Laboratory of Physiology, Faculty of Nutrition, and High-Technology Research Centre, Kobe Gakuin University, Kobe 651-2180, Japan.
Ikarugi
Hideo
H
Naemura
Aki
A
Ijiri
Yoshinobu
Y
Yamashita
Tsutomu
T
Yamamoto
Junichiro
J
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000139:chemically induced / Q000473:pathology*; D001777:Blood Coagulation / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015539:Platelet Activation / Q000187:drug effects*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D012039:Regional Blood Flow; D013927:Thrombosis / Q000139:chemically induced / Q000473:pathology*
D001057:Apolipoproteins E; D004041:Dietary Fats; D011973:Receptors, LDL