Abstract
Background: Heme oxygenase (HO) is a rate‐limiting enzyme of endogenetic carbon monoxide (CO) that degrades heme into carbon monoxide, bilirubin, and iron. These products have important physiologic effects: bilirubin is a potent antioxidant that can act against ischemia/reperfusion injury; there is a negative correlation between the content of HO‐1 and the incidence of coronary heart disease (CHD).
Hypothesis: This study was undertaken to investigate the changes of HO‐1 in patients with CHD.
Methods: Thirty‐five patients with acute myocardial infarction (AMI), 40 patients with unstable angina pectoris (UAP, diagnosed by coronary angiography), and 30 patients with stable angina pectoris (AP, diagnosed by coronary angiography) were selected for the study; another 30 patients with normal coronary artery (diagnosed by coronary angiography) were selected as controls. The levels of HO‐1 protein expression in monocyte and lymphocyte in the subjects were tested by immunohistochemistry and western blot. Computer picture analyzing systems were also used to measure the levels of HO‐1 protein expression.
Results: Heme oxygenase‐1 protein is located in cell plasma. The levels of HO‐1 protein expression in patients with CHD were significantly higher than in those without CHD (p<0.01). There were significant differences of HO‐1 expression among the three groups of patients with CHD. The group with AMI was the highest, followed by the group with UAP and finally by the group with AP.
Conclusions: There is a higher expression of HO‐1 in patients with CHD. The levels of HO‐1 protein are associated with the severity of CHD.
Keywords: heme oxygenase‐1, coronary heart disease, expression
Full Text
The Full Text of this article is available as a PDF (116.1 KB).
References
- 1. Mayer M: Association of serum bilirubin concentration with risk of coronary artery disease. Clin Chem 2000; 46 (11): 1723–1727 [PubMed] [Google Scholar]
- 2. Santiago E, Mora L, Bautista M, et al.: Granulocyte colony stimulating factor induce neutrophil to secrete macrophage colony stimulating factor [J]. Cytokin 2001; 15 (6): 299–304 [DOI] [PubMed] [Google Scholar]
- 3. Durante W: Heme oxygenase‐1 in growth control and its clinical application to vascular disease. J Cellular Physiol 2003; 195 (3): 373–382 [DOI] [PubMed] [Google Scholar]
- 4. Juan SH, Lee TS, Tseng KW, et al.: Adenovirus‐mediated hemeoxygenase‐1 gene transfer inhibits the development of atherosclerosis in apolipoprotein E‐deficient mice. Circulation 2001; 104 (13): 1519–1525 [DOI] [PubMed] [Google Scholar]
- 5. Tulis DA, Durante W, Liu X, et al.: Adenovirus‐mediated hemeoxygenase‐1 gene delivery inhibits injury‐induced vascular neointima. Circulation 2001; 104 (22): 2710–2715 [DOI] [PubMed] [Google Scholar]
- 6. Wang LJ, Lee TS, Lee FY, et al.: Expression of hemeoxygenase‐1 in atherosclerotic lesion. Am J Pathol 1998; 152 (3): 711–720 [PMC free article] [PubMed] [Google Scholar]
- 7. Li Volti G, Wang J, Traganos F, Kappas A, Abraham N: Differential effect of heme oxygenase‐1 in endothelial and smooth muscle cell cycle progression. Biochem Biophys Res Commun 2002; 296 (5): 1077–1082 [DOI] [PubMed] [Google Scholar]
- 8. Liu X, Chapman GB, Wang H, Durante W: Adenovirus‐mediated heme oxygenase‐1 gene expression stimulates apoptosis in vascular smooth muscle cells. Circulation 2002; 105: 79–84 [DOI] [PubMed] [Google Scholar]
- 9. Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S: Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase‐1 deficiency. J Clin Invest 1999; 103 (1): 129–135 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Yet S‐F, Perrella MA, Layne MD, Hsieh C‐M, Maemura K, Kobzik L, Wiesel P, Christou H, Kourembanas S, Lee M‐E: Hypoxia induces severe right ventricular dilatation and infarction in heme oxygenase‐1 null mice. J Clin Invest 1999; 103: R23–R29 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Duckers HJ, Boehm M, True AL, Yet S‐F, Park JL, Webb RC, Lee M‐E, Nabel GJ, Nabel EG: Heme oxygenase‐1 protects against vascular constriction and proliferation. Nat Med 2001; 7: 693–698 [DOI] [PubMed] [Google Scholar]
- 12. Liu X, Peyton KJ, Durante W: Heme oxygenase‐1 inhibits vascular smooth muscle cell proliferation. In Heme Oxygenase in Biology and Medicine (Eds. Abraham NG, Alam J, Nath K.), p. 439–479. New York: Kluwer Academic/Plenum Publishers, 2002. [Google Scholar]
- 13. Duckers HJ, Boehm M, True AL, Yet S‐F, Park JL, Webb RC, Lee M‐E, Nabel GJ, Nabel EG: Heme oxygenase‐1 protects against vascular constriction and proliferation. Nat Med 2001; 7: 693–698 [DOI] [PubMed] [Google Scholar]
- 14. Togane Y, Toshisuki M, Suematsu M, Ishimura Y, Yamazaki J, Katayama S: Protective roles of endogenous carbon monoxide in neointimal development elicited by arterial injury. Am J Physiol Heart Circ Physiol 2000; 278: H623–H632 [DOI] [PubMed] [Google Scholar]
- 15. Peyton KJ, Reyna SV, Chapman GB, Ensenat D, Liu X, Wang H, Schafer AI, Durante W: Heme oxygenase‐1‐derived carbon monoxide is an autocrine inhibitor of vascular smooth muscle cell growth. Blood 2002; 99: 4443–4448 [DOI] [PubMed] [Google Scholar]
- 16. Deramaudt BMJM, Braunstein S, Remy P, Abraham NG: Gene transfer of human heme oxygenase‐1 into coronary endothelial cells potentially promotes angiogenesis. J Cell Biochem 1998; 68: 121–127 [DOI] [PubMed] [Google Scholar]
- 17. Malaguarnera L, Pilastro MR, Quan S, Ghattas MH, Yang L, Mezentsev AV, Kushida T, Abraham NG, Kappas A: Significance of heme oxygenase in prolactin‐mediated cell proliferation and angiogenesis in human endothelial cells. Int J Mol Med 2002; 10: 433–440 [PubMed] [Google Scholar]