A role of oxidative stress-generated eicosanoid in the progression of arteriosclerosis in type 2 diabetes mellitus model rats.
Diabetes mellitus (DM) is a well-established risk factor of cardiovascular diseases. We investigated the mechanism of the progression of arteriosclerosis in DM, focusing on the role of oxidative stress and insulin resistance in vivo. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an experimental model of type 2 DM, were assigned to 3 groups, based on supplementation with vitamin E (VE) or troglitazone (TR), a VE-derived agent which improves insulin-resistance. At 36 weeks, plasma and aortic tissue 8-iso-PGF2alpha contents, a vascular proliferating eicosanoid produced in vivo by oxidative stress, were measured by EIA. TGF-beta1 and TGF-beta1 receptor II were immunohistochemically analyzed. Histopathologically, medial area and the nuclear number of smooth muscle cells of the aorta were measured. The tissue 8-iso-PGF2alpha content (pg/g tissue) was significantly decreased by either VE or TR in the aorta (untreated-OLETF, 15,332+/-3,254 vs. TR-treated-OLETF, 7,092+/-1,992 or VE-treated-OLETF, 5,394+/-836, both p<0.01), but that in plasma decreased by only VE. VE and TR improved the increased the level of the actual medial area and the number of smooth muscle cells. The expression of TGF-beta1 was reduced, but TGF-beta1 receptor II was not. 8-iso-PGF2alpha may play an important role in the progression of arteriosclerosis. Antioxidant treatment may promise significant clinical benefits in the early diabetic stage.
Shinomiya
Kaori
K
Second Department of Internal Medicine, Kagawa Medical University, Kagawa, Japan.
Fukunaga
Megumu
M
Kiyomoto
Hideyasu
H
Mizushige
Katsufumi
K
Tsuji
Teppei
T
Noma
Takahisa
T
Ohmori
Koji
K
Kohno
Masakazu
M
Senda
Shoichi
S
D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2; D003925:Diabetic Angiopathies / Q000473:pathology / Q000503:physiopathology*; D015237:Dinoprost / Q000031:analogs & derivatives*; D018450:Disease Progression; D015777:Eicosanoids / Q000502:physiology*; D028441:F2-Isoprostanes / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D001786:Blood Glucose; D015777:Eicosanoids; D028441:F2-Isoprostanes; D008055:Lipids; D018125:Receptors, Transforming Growth Factor beta; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost