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Heme oxygenase-1, oxidation, inflammation, and atherosclerosis.

Araujo JA, Zhang M, Yin F - Front Pharmacol (2012)

Bottom Line: HO-1 has important antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, most of which play a significant role in the protection against atherogenesis.The biological effects of HO-1 are largely attributable to its enzymatic activity, which can be conceived as a system with three arms of action, corresponding to its three enzymatic byproducts.HO-1 mediated vascular protection may be due to a combination of systemic and vascular local effects.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, CA, USA.

ABSTRACT
Atherosclerosis is an inflammatory process of the vascular wall characterized by the infiltration of lipids and inflammatory cells. Oxidative modifications of infiltrating low-density lipoproteins and induction of oxidative stress play a major role in lipid retention in the vascular wall, uptake by macrophages and generation of foam cells, a hallmark of this disorder. The vasculature has a plethora of protective resources against oxidation and inflammation, many of them regulated by the Nrf2 transcription factor. Heme oxygenase-1 (HO-1) is a Nrf2-regulated gene that plays a critical role in the prevention of vascular inflammation. It is the inducible isoform of HO, responsible for the oxidative cleavage of heme groups leading to the generation of biliverdin, carbon monoxide, and release of ferrous iron. HO-1 has important antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, most of which play a significant role in the protection against atherogenesis. HO-1 may also be an important feature in macrophage differentiation and polarization to certain subtypes. The biological effects of HO-1 are largely attributable to its enzymatic activity, which can be conceived as a system with three arms of action, corresponding to its three enzymatic byproducts. HO-1 mediated vascular protection may be due to a combination of systemic and vascular local effects. It is usually expressed at low levels but can be highly upregulated in the presence of several proatherogenic stimuli. The HO-1 system is amenable for use in the development of new therapies, some of them currently under experimental and clinical trials. Interestingly, in contrast to the HO-1 antiatherogenic actions, the expression of its transcriptional regulator Nrf2 leads to proatherogenic effects instead. This suggests that a potential intervention on HO-1 or its byproducts may need to take into account any potential alteration in the status of Nrf2 activation. This article reviews the available evidence that supports the antiatherogenic role of HO-1 as well as the potential pathways and mechanisms mediating vascular protection.

No MeSH data available.


Related in: MedlinePlus

Heme oxygenase enzymatic activity. HO enzymatic leads to the generation of biliverdin, release of carbon monoxide (CO) and Fe2+. Biliverdin is transformed into bilirubin by the biliverdin reductase (BVR) enzyme. Fe2+ can be bound by the iron storage protein ferritin.
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Figure 1: Heme oxygenase enzymatic activity. HO enzymatic leads to the generation of biliverdin, release of carbon monoxide (CO) and Fe2+. Biliverdin is transformed into bilirubin by the biliverdin reductase (BVR) enzyme. Fe2+ can be bound by the iron storage protein ferritin.

Mentions: Heme oxygenase (HO) is a rate-limiting enzyme in the catabolism of heme. In association with cytochrome P450 reductase and in the presence of NADPH and three molecules of molecular oxygen (O2) per heme molecule, it catalyzes the oxidative cleavage of heme (Fe-protoporphyrin-IX) to render equimolar amounts of biliverdin, ferrous iron (Fe2+), and carbon monoxide (CO; Maines, 1997; Figure 1). Biliverdin can then be converted to bilirubin by the cytosolic enzyme biliverdin reductase (BVR). There are three HO isoforms (HO-1, HO-2, HO-3) that have been described (Siow et al., 1999), although HO-3 may be a pseudogene derived from HO-2 transcripts (Hayashi et al., 2004). While HO-2 is constitutively expressed, HO-1 is normally expressed at low levels in most tissues but it is highly inducible by a variety of stimuli. Indeed, HO-1 may be among the most critical cytoprotective mechanisms that are activated during times of cellular stress such as inflammation, ischemia, hypoxia, hyperoxia, hyperthermia, or radiation (Choi and Alam, 1996). It is thought to play a key role in maintaining antioxidant/oxidant homeostasis and in the prevention against vascular injury (Abraham and Kappas, 2008).


Heme oxygenase-1, oxidation, inflammation, and atherosclerosis.

Araujo JA, Zhang M, Yin F - Front Pharmacol (2012)

Heme oxygenase enzymatic activity. HO enzymatic leads to the generation of biliverdin, release of carbon monoxide (CO) and Fe2+. Biliverdin is transformed into bilirubin by the biliverdin reductase (BVR) enzyme. Fe2+ can be bound by the iron storage protein ferritin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3400084&req=5

Figure 1: Heme oxygenase enzymatic activity. HO enzymatic leads to the generation of biliverdin, release of carbon monoxide (CO) and Fe2+. Biliverdin is transformed into bilirubin by the biliverdin reductase (BVR) enzyme. Fe2+ can be bound by the iron storage protein ferritin.
Mentions: Heme oxygenase (HO) is a rate-limiting enzyme in the catabolism of heme. In association with cytochrome P450 reductase and in the presence of NADPH and three molecules of molecular oxygen (O2) per heme molecule, it catalyzes the oxidative cleavage of heme (Fe-protoporphyrin-IX) to render equimolar amounts of biliverdin, ferrous iron (Fe2+), and carbon monoxide (CO; Maines, 1997; Figure 1). Biliverdin can then be converted to bilirubin by the cytosolic enzyme biliverdin reductase (BVR). There are three HO isoforms (HO-1, HO-2, HO-3) that have been described (Siow et al., 1999), although HO-3 may be a pseudogene derived from HO-2 transcripts (Hayashi et al., 2004). While HO-2 is constitutively expressed, HO-1 is normally expressed at low levels in most tissues but it is highly inducible by a variety of stimuli. Indeed, HO-1 may be among the most critical cytoprotective mechanisms that are activated during times of cellular stress such as inflammation, ischemia, hypoxia, hyperoxia, hyperthermia, or radiation (Choi and Alam, 1996). It is thought to play a key role in maintaining antioxidant/oxidant homeostasis and in the prevention against vascular injury (Abraham and Kappas, 2008).

Bottom Line: HO-1 has important antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, most of which play a significant role in the protection against atherogenesis.The biological effects of HO-1 are largely attributable to its enzymatic activity, which can be conceived as a system with three arms of action, corresponding to its three enzymatic byproducts.HO-1 mediated vascular protection may be due to a combination of systemic and vascular local effects.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, CA, USA.

ABSTRACT
Atherosclerosis is an inflammatory process of the vascular wall characterized by the infiltration of lipids and inflammatory cells. Oxidative modifications of infiltrating low-density lipoproteins and induction of oxidative stress play a major role in lipid retention in the vascular wall, uptake by macrophages and generation of foam cells, a hallmark of this disorder. The vasculature has a plethora of protective resources against oxidation and inflammation, many of them regulated by the Nrf2 transcription factor. Heme oxygenase-1 (HO-1) is a Nrf2-regulated gene that plays a critical role in the prevention of vascular inflammation. It is the inducible isoform of HO, responsible for the oxidative cleavage of heme groups leading to the generation of biliverdin, carbon monoxide, and release of ferrous iron. HO-1 has important antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, most of which play a significant role in the protection against atherogenesis. HO-1 may also be an important feature in macrophage differentiation and polarization to certain subtypes. The biological effects of HO-1 are largely attributable to its enzymatic activity, which can be conceived as a system with three arms of action, corresponding to its three enzymatic byproducts. HO-1 mediated vascular protection may be due to a combination of systemic and vascular local effects. It is usually expressed at low levels but can be highly upregulated in the presence of several proatherogenic stimuli. The HO-1 system is amenable for use in the development of new therapies, some of them currently under experimental and clinical trials. Interestingly, in contrast to the HO-1 antiatherogenic actions, the expression of its transcriptional regulator Nrf2 leads to proatherogenic effects instead. This suggests that a potential intervention on HO-1 or its byproducts may need to take into account any potential alteration in the status of Nrf2 activation. This article reviews the available evidence that supports the antiatherogenic role of HO-1 as well as the potential pathways and mechanisms mediating vascular protection.

No MeSH data available.


Related in: MedlinePlus