J Korean Med Sci.  2004 Oct;19(5):656-661. 10.3346/jkms.2004.19.5.656.

Genistein Supplementation Inhibits Atherosclerosis with Stabilization of the Lesions in Hypercholesterolemic Rabbits

• Lee CS
• Kwon SJ
• Na SY
• Lim SP
• Lee JH

• KMID: 1733504
• DOI: http://doi.org/10.3346/jkms.2004.19.5.656

Abstract

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 hypercholesterolemicrabbits. The genistein supplementation also suggests that it helps the stabilization of the atherosclerotic lesion by inhibition of MMP-3 expression.

Keyword

Arteriosclerosis; Metalloproteinases; Rabbits; Genistein; Hyperlipidemia; Diet

MeSH Terms

Animals
Aorta/pathology
Arteriosclerosis/*drug therapy/pathology/*prevention & control
Blotting, Western
Diet, Atherogenic
Genistein/*pharmacology
Growth Inhibitors/*pharmacology
Hypercholesterolemia/*drug therapy/pathology
Macrophages/pathology
Male
Muscle, Smooth, Vascular/enzymology/pathology
Rabbits
Research Support, Non-U.S. Gov't
Stromelysin 1/metabolism

Figure

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  Fig. 1 Aortic lesion development in rabbit aortas (Mean±SDs). Genistein supplementation showed reduction of the lesion size. ND, normal diet; HD, hypercholesterol diet; G, genistein; TA, thoracic aorta; AA, abdominal aorta. *p<0.05.

• 

  Fig. 2 Anti-RAM-11 immunohistochemical staining. There are strong staining of anti-RAM-11 in the superficial and deep areas of the atherosclerotic lesion. HD+G group (A), ND group (B) (×40).

• 

  Fig. 3 Anti-HHF-35 immunohistochemical staining. Mild staining of anti-HHF-35 mainly in the deep areas of the atherosclerotic lesion. HD+G group (A), ND group (B) (×40).

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  Fig. 4 The macrophage (M)/smooth muscle cell (SMC) ratio in the atherosclerotic lesion in rabbit aortas. ND, normal diet; HD, hypercholesterol diet; G, genistein.

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  Fig. 5 Inhibition of MMP-3 expression by Genstein (G) supplementation in the thoracic aorta of hypercholesterolemic rabbits. Relative optical density of MMP-3 was measured by densitometer from Western blotting. ND, normal diet; HD, hypercholesterol diet; G, genistein. *p<0.05.

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