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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1131.)
© 2001 American Heart Association, Inc.

Vascular Biology

Changes in Expression of Antioxidant Enzymes Affect Cell-Mediated LDL Oxidation and Oxidized LDL–Induced Apoptosis in Mouse Aortic Cells

ZhongMao Guo; Holly Van Remmen; Hong Yang; XinLian Chen; James Mele; Jan Vijg; Charles J. Epstein; Ye-Shih Ho; Arlan Richardson

From the Department of Physiology (Z.G., H.V., H.Y., J.V., A.R.) and the Department of Cellular and Structure Biology (X.C., J.M.), University of Texas Health Science Center at San Antonio, and the Geriatric Research, Education and Clinical Center (Z.G., H.V., A.R.), South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, Tex; the Department of Pediatrics (C.J.E.), University of California, San Francisco; and the Institute of Chemical Toxicology and Department of Biochemistry (Y.-S.H.), Wayne State University, Detroit, Mich.

Correspondence to Dr ZhongMao Guo, Department of Physiology, UTHSCSA, 7703 Floyd Curl Dr, San Antonio, TX 78229. E-mail GUO{at}uthscsa.edu

Abstract—Transgenic mice overexpressing Cu/Zn superoxide dismutase (hSod1Tg^+/0) or catalase (hCatTg^+/0) and knockout mice underexpressing manganese superoxide dismutase (Sod2^+/-) or glutathione peroxidase-1 (Gpx1^-/-) were used to study the effect of antioxidant enzymes on cell-mediated low density lipoprotein (LDL) oxidation and oxidized LDL (oxLDL)-induced apoptosis. Incubation of LDL with mouse aortic segments or smooth muscle cells (SMCs) resulted in a significant increase in LDL oxidation. However, LDL oxidation was significantly reduced when LDL was incubated with aortic segments and SMCs obtained from hSod1Tg^+/0 and hCatTg^+/0 mice compared with those obtained from wild-type mice. In contrast, LDL oxidation was significantly increased when LDL was incubated with aortic segments and SMCs obtained from Sod2^+/- and Gpx1^-/- mice. CuSO₄-oxidized LDL increased DNA fragmentation and caspase activities in the primary cultures of mouse aortic SMCs. However, oxLDL-induced DNA fragmentation and caspase activities were reduced 50% in SMCs obtained from hSod1Tg^+/0 and hCatTg^+/0 mice compared with wild-type control mice. In contrast, oxLDL-induced DNA fragmentation and caspase activities were significantly increased in SMCs obtained from Sod2^+/- and Gpx1^-/- mice. These findings suggest that overexpression of Cu/Zn superoxide dismutase or catalase reduces cell-mediated LDL oxidation and oxLDL-induced apoptosis, whereas underexpression of manganese superoxide dismutase or glutathione peroxidase-1 increases cell-mediated LDL oxidation and oxLDL-induced apoptosis.

Key Words: LDL • transgenic mice • aortas • antioxidant enzymes

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