STATE-OF-THE-ART PAPER
Hemoxygenase-1 in Cardiovascular Disease
Naglaa K. Idriss, MSc,
Andrew D. Blann, PhD and
Gregory Y.H. Lip, MD*
Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom
Manuscript received March 28, 2008;
revised manuscript received June 5, 2008,
accepted June 9, 2008.
* Reprint requests and correspondence: Dr. Gregory Y. H. Lip, City Hospital NHS Trust, University Department of Medicine, Dudley Road, City Hospital, Birmingham B18 7QH, United Kingdom (Email: g.y.h.lip{at}bham.ac.uk).
Hemoxygenase (HO)-1 is an inducible isoform of the first and rate-controlling enzyme of the degradation of heme into iron, carbon monoxide, and biliverdin, the latter being subsequently converted into bilirubin. Several positive biological effects exerted by this enzyme have gained attention, as anti-inflammatory, antiapoptotic, angiogenic, and cytoprotective functions are attributable to carbon monoxide and/or bilirubin. Thus, the physiological induction of HO-1 may be an adaptive and beneficial response to several possibly noxious stimuli, including heme itself, suggesting a potentially autoprotective and autodefensive role in several pathophysiological states including acute coronary syndromes and stroke. This review article provides a comprehensive overview of the biochemistry, physiology, and pathophysiology of HO-1 in relation to cardiovascular disease (CVD). Furthermore, we present some of the emerging evidence in support of the view that the induction of the HO-1 gene may be a new opportunity to target the pathophysiology of CVD, with therapeutic implications for management.
Key Words: cardiovascular disease • hemoxygenase-1 • heme • bilirubin • carbon monoxide
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Abbreviations and Acronyms
| | CAD = coronary artery disease | | cGMP = cyclic guanine monophosphate | | CO = carbon monoxide | | CVD = cardiovascular disease | | GT = glutathione thymidine dinucleotide | | HO = hemoxygenase | | NO = nitric oxide | | VEGF = vascular endothelial growth factor |
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