scholarly journals The Protective Role of Heme Oxygenase-1 in Atherosclerotic Diseases

2019 ◽  
Vol 20 (15) ◽  
pp. 3628 ◽  
Author(s):  
Yoshimi Kishimoto ◽  
Kazuo Kondo ◽  
Yukihiko Momiyama
Keyword(s):  
Animal Models ◽  
Heme Oxygenase ◽  
Protective Role ◽  
Heme Oxygenase 1 ◽  
Intracellular Enzyme ◽  
Anti Oxidant ◽  
Low Levels ◽  
Artery Disease ◽  
Accelerate Atherosclerosis

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.

scholarly journals Plasma Heme Oxygenase-1 Levels in Patients with Coronary and Peripheral Artery Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yoshimi Kishimoto ◽  
Susumu Ibe ◽  
Emi Saita ◽  
Kenji Sasaki ◽  
Hanako Niki ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Ankle Brachial Index ◽  
Protective Role ◽  
Heme Oxygenase 1 ◽  
Peripheral Artery ◽  
Intracellular Enzyme ◽  
Vessel Disease ◽  
Artery Disease ◽  
Peripheral Artery Diseases ◽  
Progression Of Atherosclerosis

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.

scholarly journals A Dual Role of Heme Oxygenase-1 in Cancer Cells

2018 ◽  
Vol 20 (1) ◽  
pp. 39 ◽  
Author(s):  
Shih-Kai Chiang ◽  
Shuen-Ei Chen ◽  
Ling-Chu Chang
Keyword(s):  
Cell Death ◽  
Heme Oxygenase ◽  
Cancer Progression ◽  
Critical Role ◽  
Causative Factor ◽  
Protective Role ◽  
Dark Side ◽  
Heme Oxygenase 1 ◽  
Cellular Iron

Heme oxygenase (HO)-1 is known to metabolize heme into biliverdin/bilirubin, carbon monoxide, and ferrous iron, and it has been suggested to demonstrate cytoprotective effects against various stress-related conditions. HO-1 is commonly regarded as a survival molecule, exerting an important role in cancer progression and its inhibition is considered beneficial in a number of cancers. However, increasing studies have shown a dark side of HO-1, in which HO-1 acts as a critical mediator in ferroptosis induction and plays a causative factor for the progression of several diseases. Ferroptosis is a newly identified iron- and lipid peroxidation-dependent cell death. The critical role of HO-1 in heme metabolism makes it an important candidate to mediate protective or detrimental effects via ferroptosis induction. This review summarizes the current understanding on the regulatory mechanisms of HO-1 in ferroptosis. The amount of cellular iron and reactive oxygen species (ROS) is the determinative momentum for the role of HO-1, in which excessive cellular iron and ROS tend to enforce HO-1 from a protective role to a perpetrator. Despite the dark side that is related to cell death, there is a prospective application of HO-1 to mediate ferroptosis for cancer therapy as a chemotherapeutic strategy against tumors.

scholarly journals Autophagic proteins regulate cigarette smoke induced apoptosis: Protective role of heme oxygenase-1

Autophagy ◽  
2008 ◽  
Vol 4 (7) ◽  
pp. 887-895 ◽  
Author(s):  
Hong Pyo Kim ◽  
Xue Wang ◽  
Seon-Jin Lee ◽  
Min-Hsin Huang ◽  
Yong Wan ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Heme Oxygenase ◽  
Protective Role ◽  
Heme Oxygenase 1 ◽  
Induced Apoptosis ◽  
Autophagic Proteins

PROTECTIVE ROLE OF HEME OXYGENASE 1 IN THE INTESTINAL TISSUE INJURY IN HEMORRHAGIC SHOCK IN RATS

Shock ◽  
2008 ◽  
Vol 29 (2) ◽  
pp. 252-261 ◽  
Author(s):  
Kazuyoshi Inoue ◽  
Toru Takahashi ◽  
Kenji Uehara ◽  
Hiroko Shimuzu ◽  
Kana Ido ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Heme Oxygenase ◽  
Tissue Injury ◽  
Protective Role ◽  
Heme Oxygenase 1 ◽  
Intestinal Tissue

scholarly journals Inductive transcription and protective role of fish heme oxygenase-1 under hypoxic stress

2008 ◽  
Vol 211 (16) ◽  
pp. 2700-2706 ◽  
Author(s):  
D. Wang ◽  
X.-P. Zhong ◽  
Z.-X. Qiao ◽  
J.-F. Gui
Keyword(s):  
Heme Oxygenase ◽  
Protective Role ◽  
Heme Oxygenase 1 ◽  
Hypoxic Stress

scholarly journals The Diverse Roles of Heme Oxygenase-1 in Tumor Progression

2021 ◽  
Vol 12 ◽  
Author(s):  
Kim Ngan Luu Hoang ◽  
Joanne E. Anstee ◽  
James N. Arnold
Keyword(s):  
Tumor Progression ◽  
Heme Oxygenase ◽  
Cancer Progression ◽  
Biologically Active ◽  
Heme Oxygenase 1 ◽  
Biological Processes ◽  
Intracellular Enzyme ◽  
Promising Therapeutic Approach ◽  
Anti Inflammation

Heme oxygenase-1 (HO-1) is an inducible intracellular enzyme that is expressed in response to a variety of stimuli to degrade heme, which generates the biologically active catabolites carbon monoxide (CO), biliverdin and ferrous iron (Fe2+). HO-1 is expressed across a range of cancers and has been demonstrated to promote tumor progression through a variety of mechanisms. HO-1 can be expressed in a variety of cells within the tumor microenvironment (TME), including both the malignant tumor cells as well as stromal cell populations such as macrophages, dendritic cells and regulatory T-cells. Intrinsically to the cell, HO-1 activity provides antioxidant, anti-apoptotic and cytoprotective effects via its catabolites as well as clearing toxic intracellular heme. However, the catabolites of heme degradation can also diffuse outside of the cell to extrinsically modulate the wider TME, influencing cellular functionality and biological processes which promote tumor progression, such as facilitating angiogenesis and metastasis, as well as promoting anti-inflammation and immune suppression. Pharmacological inhibition of HO-1 has been demonstrated to be a promising therapeutic approach to promote anti-tumor immune responses and inhibit metastasis. However, these biological functions might be context, TME and cell type-dependent as there is also conflicting reports for HO-1 activity facilitating anti-tumoral processes. This review will consider our current understanding of the role of HO-1 in cancer progression and as a therapeutic target in cancer.

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