Prevention of atherosclerotic plaque rupture by the regulation of oxygen radical metabolism of vascular wall cells.

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Recent studies revealed that myocardial infarction is not occurred from highly progressive atherosclerotic lesions, but rather from relatively mild lesions. Therefore, prevention of rupture of unstable coronary plaque is necessary for the prevention of acute myocardial infarction. In this study, we examined whether regulation of oxygen radical in vascular smooth muscle cells can modulate stability of atherosclerotic plaque. In the first year, we demonstrated that antioxidative enzyme, Mn-SOS, was induced in cultured vascular smooth muscle cells by the preconditioning with heat shock or TNF-α together with the acquisition of tolerance to oxidative stress. In the second year, we revealed that the induction of Mn-SOD by TNF-α was inhibited by the addition of antisenseoligodeoxyribonucleotide (AODN) to Mn-SOD and that the tolerance to oxidative stress was also abolished by the treatment with AODN. On the other hand, lipofection of Mn-SOD to smooth muscle cells introduced Mn-SOD in mitochondria of cells and augmented tolerance to oxidative stress. These results suggest that the expression of antioxidative enzyme in vascular wall cells is closely related to the survival of smooth muscle cells and that by introducing antioxidative enzyme in cells could stabilize atherosclerotic plaque.