Genistein supplementation inhibits atherosclerosis with stabilization of the lesions in hypercholesterolemic rabbits.
The effect of genistein on aortic atherosclerosis was studied by immunohistochemistry with RAM-11 and HHF-35 antibodies and western blotting for matrix metalloproteinase-3 (MMP-3) in New Zealand White rabbits. After provocation of atherosclerosis with hyperlipidemic diet, the rabbits were divided as hyperlipidemic diet group (HD), normal diet group (ND) and hyperlipidemic plus genistein diet group (HD+genistein) for 4 and half months. The average cross sectional area of atherosclerotic lesion was 0.269 mm2 after provocation. The lesion was progressed by continuous hyperlipidemic diet (10.06 mm2) but was increased mildly by genistein (0.997 mm2), and decreased by normal diet (0.228 mm2). The ratio of macrophages to smooth muscle cells in the lesion was not changed by genistein supplementation. The western blotting showed reduction of MMP-3 expression in HD+genistein and ND groups than HD group. The inhibition of atherogenesis by genistein was might be due to improve the endothelial dysfunction rather than direct action on macrophages and/or smooth muscle cells in the lesion, since endothelial dysfunction by lipid peroxidation was the main atherogenic factor in the hypercholesterolemic rabbits. The genistein supplementation also suggests that it helps the stabilization of the atherosclerotic lesion by inhibition of MMP-3 expression.
Lee
Choong-Sik
CS
Department of Pathology, Chungnam National University College of Medicine, Daejeon, Korea. cslee@cnu.ac.kr.
Kwon
Su-Jin
SJ
Na
Sun-Young
SY
Lim
Seung-Pyung
SP
Lee
Jung-Hee
JH
D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D015153:Blotting, Western; D004036:Diet, Atherogenic; D019833:Genistein / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology; D011817:Rabbits
D006131:Growth Inhibitors; D019833:Genistein; D019278:Matrix Metalloproteinase 3