Heme oxygenase-1 inhibits progression and destabilization of vulnerable plaques in a rabbit model of atherosclerosis

Li, Tingting; Tian, Hongbo; Zhao, Yu-xia; An, Fengshuang; Zhang, Lei; Zhang, Jianning; Peng, Jie; Zhang, Yun; Guo, Yuan

doi:10.1016/j.ejphar.2011.09.188

Cited by 30 publications

(25 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, pharmacological manipulation of the gene results in similar effects. Thus, administration of hemin results in significant HO-1 upregulation and decreased atherogenesis in LDLR −/− mice (Ishikawa et al, 2001b), ApoE −/− mice (Cheng et al, 2009), and rabbits fed a high fat diet (Li et al, 2011; Liu et al, 2012). Since increased expression of HO-1 carries the danger of increased release of ferrous iron (Fe 2+ ) and exacerbation of iron-mediated ROS formation, Ishikawa et al (2001b) administered iron-chelating deferoxamine to LDLR −/− mice that were treated with hemin to avoid this potential problem.…”

Section: Role Of Ho-1 and Other Antioxidant Genes In Atherosclerosismentioning

confidence: 99%

“…Since increased expression of HO-1 carries the danger of increased release of ferrous iron (Fe 2+ ) and exacerbation of iron-mediated ROS formation, Ishikawa et al (2001b) administered iron-chelating deferoxamine to LDLR −/− mice that were treated with hemin to avoid this potential problem. However, subsequent studies in ApoE −/− mice and rabbits showed that this was not necessary (Cheng et al, 2009; Li et al, 2011; Liu et al, 2012). This is likely due to the fact that HO-1 upregulation colocalizes with increased expression of ferritin in atherosclerotic lesions, which may ensure safe disposal of the released Fe 2+ .…”

Section: Role Of Ho-1 and Other Antioxidant Genes In Atherosclerosismentioning

confidence: 99%

See 1 more Smart Citation

Heme Oxygenase-1, Oxidation, Inflammation, and Atherosclerosis

Araujo¹,

Zhang²,

Yin³

2012

Front. Pharmacol.

363

263

View full text Add to dashboard Cite

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.

show abstract

Section: Role Of Ho-1 and Other Antioxidant Genes In Atherosclerosismentioning

confidence: 99%

Section: Role Of Ho-1 and Other Antioxidant Genes In Atherosclerosismentioning

confidence: 99%

Heme Oxygenase-1, Oxidation, Inflammation, and Atherosclerosis

Araujo¹,

Zhang²,

Yin³

2012

Front. Pharmacol.

363

263

View full text Add to dashboard Cite

show abstract

“…One promising approach is the use of pharmacological inducers. Heme and its synthetic analogues as potent inducers of HO-1 have been proved to protect against the development of vascular disease in numerous studies (13,20,21). …”

Section: Introductionmentioning

confidence: 99%

Anti-oxidant effect of heme oxygenase-1 on cigarette smoke-induced vascular injury

Yang

et al. 2015

Molecular Medicine Reports

View full text Add to dashboard Cite

Cigarette smoking, a major independent risk factor of atherosclerosis, can cause oxidative and inflammatory damage of vascular tissue. Heme oxygenase-1 (HO-1) is an endogenous cytoprotective enzyme with an anti-oxidant role in cells. The aim of the present study was to investigate whether HO-1 was able to protect vascular and endothelial cells from the oxidative damage induced by cigarette smoking. It was observed that cigarette smoking was able to induce the generation of the reactive oxygen species (ROS) in carotid arteries of rats. Hemin, a widely used HO-1 inducer, was able to reduce the generation of ROS. In addition, when human umbilical vein endothelial cells (HUVECs) were cultured in the serum of smoking rats, this was able to increase ROS, and the protective effect of hemin was also observed in this system. In conclusion, the present study demonstrated that cigarette smoking causes oxidative damage of vascular cells and HUVECs by inducing the generation of ROS, while HO-1 has an anti-oxidant effect in this course. This also implied that hemin, an inducer of HO-1, may have potential therapeutic applicability in the prevention of vascular diseases caused by cigarette smoking.

show abstract

“…Furthermore, HO-1 is currently regarded as a novel therapeutic target in the treatment of vascular disease, and several strategies have been employed to target this enzyme in the vasculature. A variety of pharmacological agents of different chemical structures have been shown to protect against the development of vascular disease in numerous studies in vivo [7,8]. Moreover, Yang et al [9] demonstrated the anti-oxidant protective role of HO-1 in vitro by reducing endogenous reactive oxygen species (ROS) production in HUVECs when grown in serum from rats exposed to cigarette smoke [9].…”

Section: Introductionmentioning

confidence: 99%

Heme oxygenase (HO)-1 induction prevents Endoplasmic Reticulum stress-mediated endothelial cell death and impaired angiogenic capacity

Maamoun

Zachariah

McVey

et al. 2017

Biochemical Pharmacology

View full text Add to dashboard Cite

Most of diabetic cardiovascular complications are attributed to endothelial dysfunction and impaired angiogenesis. Endoplasmic Reticulum (ER) and oxidative stresses were shown to play a pivotal role in the development of endothelial dysfunction in diabetes.Hemeoxygenase-1 (HO-1) was shown to protect against oxidative stress in diabetes; however, its role in alleviating ER stress-induced endothelial dysfunction remains not fully elucidated. We aim here to test the protective role of HO-1 against high glucose-mediated ER stress and endothelial dysfunction and understand the underlying mechanisms with special emphasis on oxidative stress, inflammation and cell death. Altogether, we show here the critical role of ER stress-mediated cell death in diabetesinduced endothelial dysfunction and impaired angiogenesis and underscore the role of HO-1 induction as a key therapeutic modulator for ER stress response in ischemic disorders and diabetes. Our results also highlight the complex interplay between ER stress response and oxidative stress.

show abstract

Heme oxygenase-1 inhibits progression and destabilization of vulnerable plaques in a rabbit model of atherosclerosis

Cited by 30 publications

References 38 publications

Heme Oxygenase-1, Oxidation, Inflammation, and Atherosclerosis

Heme Oxygenase-1, Oxidation, Inflammation, and Atherosclerosis

Anti-oxidant effect of heme oxygenase-1 on cigarette smoke-induced vascular injury

Heme oxygenase (HO)-1 induction prevents Endoplasmic Reticulum stress-mediated endothelial cell death and impaired angiogenic capacity

Contact Info

Product

Resources

About