Effect of infarcted myocardium on diagnostic accuracy of exercise echocardiography for detecting noninfarct-related coronary artery lesions

Background The utility of exercise echocardiography for evaluating remote ischemia due to noninfarct-related artery (n-IRA) lesions in patients with prior myocardial infarction has not been established.Methods Quantitative coronary angiography and treadmill exercise echocardiography were performed within 2 weeks in 115 patients with prior myocardial infarction (>6 weeks) and 224 patients without myocardial infarction. Coronary lumen diameter stenosis ≥50% (by angiography) and the lack of a hyperdynamic response on exercise echocardiography were considered significant. Myocardial infarction size was defined as the number of myocardial segments with severe hypokinesis, akinesis, or dyskinesis on echocardiography at rest.Results For detection of n-IRA lesions in patients with prior myocardial infarction, the sensitivity of exercise echocardiography was similar (78% vs 79%, P = not significant), however, the specificity was significantly lower (77% vs 91%, P < .01) than for detection of significant stenoses in patients without prior myocardial infarction. Angiographic percent-diameter stenosis, presence of collateral vessel, achieved exercise level, and presence of peri-infarct ischemia did not affect the specificity of exercise echocardiography. However, the specificity of exercise echocardiography was significantly lower (69% vs 84%, P < .05) in patients with echocardiographically large infarction (infarction size ≥2) than in patients with small infarction (infarction size <2).Conclusion In patients with prior myocardial infarction, exercise echocardiography showed low specificity for detection of noninfarct-related artery lesions, especially in patients with echocardiographically large myocardial infarction. These characteristics of treadmill exercise echocardiography should be considered when this technique is applied for patients with healed myocardial infarction. (Am Heart J 2003;145:162-8.)     

Dihydrotestosterone inhibits lectin-like oxidized-LDL receptor-1 expression in aortic endothelial cells via a NF-κB/AP-1-mediated mechanism

The mechanisms involved in the antiatherosclerotic effects of androgens are unclear. Although lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in endothelial cells plays critical roles in atherosclerosis, the effects of androgens on endothelial LOX-1 expression has not been examined. Therefore, to investigate the effects of dihydrotestosterone (DHT) on LOX-1 expression in rabbit aortic endothelial cells and cultured human aortic endothelial cells (HAEC), pellets containing DHT or placebo were s.c. implanted into 26 male New Zealand white rabbits at the time of castration or sham operation. The rabbits were then fed a high-cholesterol diet (HCD) for 2 wk. Microscopic examination of the aortic arch revealed that DHT significantly reduced HCD-induced LOX-1 expression in endothelial cells compared with placebo. In cultured HAEC, DHT at concentrations above 10(-9) to 10(-7) mol/liter inhibited TNFα-induced LOX-1 mRNA and protein expression. Deletion and mutation analysis of human LOX-1 promoter-luciferase constructs transfected into HAEC with an androgen receptor (AR) expression plasmid revealed that the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element (TRE; nucleotides -60/-53) contributed to the inhibitory effects of DHT on TNFα-induced LOX-1 expression. Chromatin immunoprecipitation (ChIP) and re-ChIP assays revealed that TNFα- and TPA-dependent enrichment of p65 and phosphorylated c-Jun in the TRE chromatin region was inhibited by DHT-AR. Consistent with these results, DHT also suppressed TPA-induced expression of LOX-1. In conclusion, DHT exerts antiatherosclerotic effects by suppressing endothelial LOX-1 expression. This effect is partly mediated by the suppression of nuclear factor-κB- and activator protein 1-dependent activation of the LOX-1 promoter.