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-PGF(2alpha) contents, a vascular proliferating eicosanoid produced in vivo by oxidative stress, were measured by EIA. TGF-beta(1) and TGF-beta(1) 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-PGF(2alpha) 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-β(1) was reduced, but TGF-β(1) receptor II was not. 8-iso-PGF(2α) may play an important role in the progression of arteriosclerosis. Antioxidant treatment may promise significant clinical benefits in the early diabetic stage.