Abstract
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.
Highlights
Atherosclerotic diseases are known to be the leading causes of death in the world
These cells move into the wall of the artery and are transformed into foam cells by uptake of modified low-density lipoprotein (LDL) such as oxidized LDL, which collect cholesterol and other fatty materials and trigger smooth muscle cells to migrate from the media to the intima
This review documents the roles of Heme oxygenase-1 (HO-1) in atherosclerosis and focuses on the clinical significance as a potential therapeutic target in atherosclerotic diseases, such as coronary artery disease (CAD) and peripheral artery disease (PAD)
Summary
Atherosclerosis begins when the injured (or activated) artery wall creates chemical signals that cause certain types of leukocytes to attach to the endothelium [1] These cells move into the wall of the artery and are transformed into foam cells by uptake of modified low-density lipoprotein (LDL) such as oxidized LDL, which collect cholesterol and other fatty materials and trigger smooth muscle cells to migrate from the media to the intima. HO-1, known as a 32-kDa heat shock protein, encoded by the gene HMOX1, is normally expressed at low levels in most tissues; HO-1 is highly inducible in response to various stresses/stimuli, including heme/hemoglobin, heavy metals, UV radiation, cytokines, and endotoxins [8,9,10,11,12]. HO-1 protein expression was higher in patients with CAD (AMI > UAP > SAP > Control). SAP, stable angina pectoris; UAP, unstable angina pectoris; AMI, acute myocardial infarction; CAD, coronary artery disease; ACS, acute coronary syndrome; PAD, peripheral artery disease; TIA, transient ischemic attack
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