Heme oxygenase is a rate-limiting enzyme in heme degradation, leading to the generation of free iron, biliverdin, and carbon monoxide. Induction of heme oxygenase-1 is implicated in the antioxidant defense mechanism and can modulate vascular function. To test the association of microsatellite polymorphism in the promoter region of human HO-1 gene with the risk of coronary artery disease (CAD) in type 2 diabetic patients, we examined the allele frequencies of (GT) (n) repeats in HO-1 gene in 474 patients with CAD and in 322 controls. A transient-transfection assay with HO-1 promoter/luciferase fusion constructs carrying various lengths of (GT) (n) repeats was performed to explore the regulatory effect of (GT) (n) repeats on HO-1 gene expression in cultured rat aortic smooth muscle cells. Serum thiobarbituric acid-reactive substances (TBARs), a measure of lipid peroxidation, was significantly higher in subjects carrying the L/L genotype (> or =32 repeats). Among type 2 diabetic subjects, the frequencies of the L alleles and proportion of genotypes with L alleles were significantly higher in those with CAD than in those without CAD. The adjusted odds ratio for CAD in type 2 diabetic patients with L alleles was 4.7 (95% confidence interval, 1.9-12.0, P=0.001). Transfection experiments in aortic smooth muscle cells revealed that HO-1 promoter/luciferase fusion constructs containing longer (GT) (n) repeats exhibited lower transcriptional activity. These results imply that the length polymorphism in the HO-1 gene promoter modulate the transcription of the gene in vascular cells. Type 2 diabetics carrying longer (GT) (n) repeats might have higher oxidative stress and increased susceptibility to the development of CAD.

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Current noninvasive techniques for assessing central aortic pressure require the recording of an arterial pressure wave using a high-fidelity applanation tonometer. We therefore developed and validated a novel method to estimate the central aortic systolic pressure using an oscillometric blood pressure monitor alone. Invasive high-fidelity right brachial and central aortic pressure waves, and left-brachial pulse volume plethysmography from an oscillometric blood pressure monitor, were obtained at baseline and 3 min after administration of sublingual nitroglycerin in 100 patients during cardiac catheterization. In the initial 50 patients (Generation Group), Central systolic blood pressure was predicted by a multi-variate prediction model generated from the comprehensive analysis of the invasive brachial pressure wave, including brachial late-systolic shoulder pressure value and parameters related to wave reflection and arterial compliance. Another prediction model was similarly constructed from the noninvasively calibrated pulse volume plethysmography. Both models were validated in the subsequent 50 patients (Validation Group) with results: r¼0.98 (Po0.001) and mean difference¼0.5±4.5 (95% confidence interval À8.3 to 9.3) mm Hg for the invasive model, and r¼0.93 (Po0.001) and mean difference¼À0.1 ± 7.6 (95% confidence interval À15.0 to 14.8) mm Hg for the noninvasive model. Thus, our results indicate that central aortic systolic blood pressure could be estimated by analysis of the noninvasive brachial pressure wave alone from an oscillometric blood pressure monitor.

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