The Protective Role of Heme Oxygenase-1 in Atherosclerotic Diseases

• Published in: International journal of molecular sciences 2019-07, Vol.20 (15), p.3628
• Main Authors: Kishimoto, Yoshimi, Kondo, Kazuo, Momiyama, Yukihiko
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Anemia; Animals; Antioxidants; Arteriosclerosis; Atherosclerosis; Atherosclerosis - blood; Atherosclerosis - genetics; Atherosclerosis - pathology; Atherosclerosis - prevention & control; Bilirubin; Biliverdine - metabolism; Carbon Monoxide - metabolism; Cardiovascular disease; Cell membranes; Coronary Artery Disease - blood; Coronary Artery Disease - genetics; Coronary Artery Disease - pathology; Coronary Artery Disease - prevention & control; Endothelium; Free radicals; Genotype & phenotype; Glycogen; Glycogen synthase kinase 3; Glycogens; Heme; Heme - metabolism; Heme oxygenase (decyclizing); Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - therapeutic use; Humans; Inflammation; Iron; Iron - metabolism; Kinases; Lipid peroxidation; Lipids; Lipophilic; Low density lipoprotein; MAP kinase; Oxidants; Oxidation; Oxidative stress; Oxidizing agents; Oxygenase; Pathogenesis; Peripheral Arterial Disease - blood; Peripheral Arterial Disease - genetics; Peripheral Arterial Disease - pathology; Peripheral Arterial Disease - prevention & control; Peroxy radicals; Phosphorylation; Physiology; Polymorphism; Protein kinase C; Proteins; Reactive Oxygen Species - metabolism; Review; Serine; Singlet oxygen; Transcription factors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20153628

Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme to generate ferrous iron, carbon monoxide (CO), and biliverdin, which is subsequently converted to bilirubin. These products have anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-thrombotic properties. Although HO-1 is expressed at low levels in most tissues under basal conditions, it is highly inducible in response to various pathophysiological stresses/stimuli. HO-1 induction is thus thought to be an adaptive defense system that functions to protect cells and tissues against injury in many disease settings. In atherosclerosis, HO-1 may play a protective role against the progression of atherosclerosis, mainly due to the degradation of pro-oxidant heme, the generation of anti-oxidants biliverdin and bilirubin and the production of vasodilator CO. In animal models, a lack of HO-1 was shown to accelerate atherosclerosis, whereas HO-1 induction reduced atherosclerosis. It was also reported that HO-1 induction improved the cardiac function and postinfarction survival in animal models of heart failure or myocardial infarction. Recently, we and others examined blood HO-1 levels in patients with atherosclerotic diseases, e.g., coronary artery disease (CAD) and peripheral artery disease (PAD). Taken together, these findings to date support the notion that HO-1 plays a protective role against the progression of atherosclerotic diseases. This review summarizes the roles of HO-1 in atherosclerosis and focuses on the clinical studies that examined the relationships between HO-1 levels and atherosclerotic diseases.