Abstract
Aims Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme to generate CO, biliverdin, and iron. Since these products have antiatherogenic properties, HO-1 may play a protective role against the progression of atherosclerosis. However, plasma HO-1 levels in patients with atherosclerotic diseases, such as coronary artery disease (CAD) and peripheral artery disease (PAD), have not been clarified yet. Methods We investigated plasma HO-1 levels by ELISA in 410 consecutive patients undergoing elective coronary angiography who also had an ankle-brachial index (ABI) test for PAD screening. Results Of the 410 study patients, CAD was present in 225 patients (55%) (1-vessel (1-VD), n = 91; 2-vessel (2-VD), n = 66; 3-vessel disease (3-VD), n = 68). PAD (ABI < 0.9) was found in 36 (9%) patients. Plasma HO-1 levels did not differ between 225 patients with CAD and 185 without CAD (median 0.44 versus 0.35 ng/mL), but they were significantly lower in 36 patients with PAD than in 374 without PAD (0.27 versus 0.41 ng/mL, P < 0.02). After excluding the 36 patients with PAD, HO-1 levels were significantly higher in 192 patients with CAD than in 182 without CAD (0.45 versus 0.35 ng/mL, P < 0.05). HO-1 levels in 4 groups of CAD(−), 1-VD, 2-VD, and 3-VD were 0.35, 0.49, 0.44, and 0.44 ng/mL, respectively, and were highest in 1-VD (P < 0.05). In the multivariate analysis, HO-1 levels were inversely associated with PAD, whereas they were also associated with CAD. The odds ratios for PAD and CAD were 2.12 (95% CI = 1.03–4.37) and 0.65 (95% CI = 0.42–0.99) for the HO-1 level of <0.35 ng/mL, respectively. Conclusions Plasma HO-1 levels were found to be low in patients with PAD, in contrast to high levels in patients with CAD.
Highlights
Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme to generate carbon monoxide (CO), biliverdin, and ferrous iron
Plasma HO-1 levels did not differ between patients with coronary artery disease (CAD) and those without CAD, whereas they were significantly lower in patients with peripheral artery disease (PAD) than in those without PAD
After excluding patients with PAD, HO-1 levels were significantly higher in patients with CAD than in those without CAD and were highest in 1-VD among the 4 groups of CAD(−), 1-VD, 2-vessel disease (2-VD), and 3-vessel disease (3-VD)
Summary
Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme to generate carbon monoxide (CO), biliverdin, and ferrous iron. These products have anti-inflammatory, antioxidant, antiapoptotic, and antithrombotic properties [1]. HO-1 is considered to have protective properties against the development of atherosclerosis, mainly due to the degradation of prooxidant heme, the generation of antioxidant biliverdin, and the production of vasodilator CO [2]. The HO-1 expression was observed throughout the development of atherosclerotic lesions from early fatty streaks to advanced lesions [3]. HO-1 expression in atherosclerotic lesions is considered to be a protective response against the progression of atherosclerosis
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