Endothelial dysfunction induced by oxidized low-density lipoproteins in isolated mouse aorta: a comparison with apolipoprotein-E deficient mice

Abstract

We characterized the acute effects of oxidized low-density lipoproteins (oxidized-LDL) on vascular reactivity in isolated aorta from wild-type C57BL/6J mice, and compared these with the chronic alterations in vascular function observed in apolipoprotein-E gene knockout [ApoE(−/−)] mice fed a high-fat diet, which results in hyperlipidemia and atherosclerosis. In the abdominal (but not thoracic) aorta, oxidized-LDL (100 μg/ml) reduced relaxations induced by acetylcholine (10 −9 M–10 −5 M), which are mediated entirely by nitric oxide (NO). The relaxations induced by the NO donor S-nitroso- N-acetylpenicillamine (SNAP, 10 −8 M–10 −4 M), the cyclic GMP analogue 8-bromo cyclic GMP (100 μM) and the nonspecific vasodilator papaverine (100 μM) were not changed by oxidized-LDL. Native LDL had no effect on vasorelaxations. The attenuation of endothelium-dependent relaxations caused by oxidized-LDL mimicked the endothelial dysfunction found in ApoE(−/−) mice. These results are consistent with the suggestion that oxidized-LDL has an important role in the pathogenesis of endothelial NO dysfunction associated with hyperlipidemia and atherosclerosis in these mice.