Increased atherosclerosis in hyperlipidemic mice deficient in alpha -tocopherol transfer protein and vitamin E.

Although lipid peroxidation in the subendothelial space has been hypothesized to play a central role in atherogenesis, the role of vitamin E in preventing lipid peroxidation and lesion development remains uncertain. Here we show that in atherosclerosis-susceptible apolipoprotein E knockout mice, vitamin E deficiency caused by disruption of the alpha-tocopherol transfer protein gene (Ttpa) increased the severity of atherosclerotic lesions in the proximal aorta. The increase was associated with increased levels of isoprostanes, a marker of lipid peroxidation, in aortic tissue. These results show that vitamin E deficiency promotes atherosclerosis in a susceptible setting and support the hypothesis that lipid peroxidation contributes to lesion development. Ttpa(-/-) mice are a genetic model of vitamin E deficiency and should be valuable for studying other diseases in which oxidative stress is thought to play a role.

Reversal of segmental hypokinesis by coronary angioplasty in patients with unstable angina, persistent T wave inversion, and left anterior descending coronary artery stenosis. Additional evidence for myocardial stunning in humans.

To evaluate the significance of persistent negative T waves during severe ischemia, we prospectively studied 62 patients admitted for unstable angina without evidence of recent or ongoing myocardial infarction. A critical stenosis on the left anterior descending coronary artery (LAD), considered as the culprit lesion, was successfully treated by percutaneous transluminal coronary angioplasty (PTCA). The patients were divided into two groups according to the admission electrocardiogram: T NEG group (n = 32) had persistent negative T waves, and the T POS group (n = 30) had normal positive T waves on precordial leads. The two groups had similar baseline clinical, hemodynamic, and angiographic characteristics. All patients underwent a complete clinical and angiographic evaluation (coronary arteriography and left ventriculography) before undergoing PTCA and 8 +/- 3 months later. Left ventricular anterior wall motion was evaluated by the percent shortening of three areas (S1, S2, and S3) considered as LAD-related segments on left ventriculograms. Before PTCA, there was no significant difference in global ejection fraction between the two groups despite a significant depression in anterior mean percent area shortening in the T NEG compared with the T POS group (S1, 44 versus 54, p less than 0.01; S2, 39 versus 48, p less than 0.01; S3, 44 versus 50, NS). At repeated angiography, the anterior mean percent area shortening improved significantly in the T NEG group (S1, from 44 to 61, p less than 0.001; S2, from 39 to 58, p less than 0.001; S3, from 44 to 61, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)