Ablation of the Bach1 Gene Leads to the Suppression of Atherosclerosis in Bach1 and Apolipoprotein E Double Knockout Mice

Watari, Yuichiro; Yamamoto, Yoshiyuki; Brydun, Andrey; Ishida, Takafumi; Mito, Shinji; Yoshizumi, Masao; Igarashi, Kazuhiko; Chayama, Kazuaki; Ohshima, T; Ozono, Ryoji

doi:10.1291/hypres.31.783

Cited by 47 publications

(36 citation statements)

References 39 publications

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“…Consequently, deletion of the bach1 gene leads to sustained HO-1 expression in various tissues. The effect of bach1 deletion in atherosclerosis was studied in Bach1 apoE double deficient mice (Watari et al, 2008). In these mice HO-1 was upregulated in the vasculature, mainly in the vascular endothelium (Watari et al, 2008).…”

Section: Altered Iron Homeostasis and Atherosclerosis: Animal Modelsmentioning

confidence: 99%

“…The effect of bach1 deletion in atherosclerosis was studied in Bach1 apoE double deficient mice (Watari et al, 2008). In these mice HO-1 was upregulated in the vasculature, mainly in the vascular endothelium (Watari et al, 2008). Elevated HO-1 expression was accompanied by reduced plaque area compared with that in apoE deficient mice, supporting the anti-atherogenic nature of HO-1 (Watari et al, 2008).…”

Section: Altered Iron Homeostasis and Atherosclerosis: Animal Modelsmentioning

confidence: 99%

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Atherogenesis and iron: from epidemiology to cellular level

et al. 2014

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Iron accumulates in human atherosclerotic lesions but whether it is a cause or simply a downstream consequence of the atheroma formation has been an open question for decades. According to the so called “iron hypothesis,” iron is believed to be detrimental for the cardiovascular system, thus promoting atherosclerosis development and progression. Iron, in its catalytically active form, can participate in the generation of reactive oxygen species and induce lipid-peroxidation, triggering endothelial activation, smooth muscle cell proliferation and macrophage activation; all of these processes are considered to be proatherogenic. On the other hand, the observation that hemochromatotic patients, affected by life-long iron overload, do not show any increased incidence of atherosclerosis is perceived as the most convincing evidence against the “iron hypothesis.” Epidemiological studies and data from animal models provided conflicting evidences about the role of iron in atherogenesis. Therefore, more careful studies are needed in which issues like the source and the compartmentalization of iron will be addressed. This review article summarizes what we have learnt about iron and atherosclerosis from epidemiological studies, animal models and cellular systems and highlights the rather contributory than innocent role of iron in atherogenesis.

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Section: Altered Iron Homeostasis and Atherosclerosis: Animal Modelsmentioning

confidence: 99%

Section: Altered Iron Homeostasis and Atherosclerosis: Animal Modelsmentioning

confidence: 99%

Atherogenesis and iron: from epidemiology to cellular level

et al. 2014

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“…6,56 Although to date there are no reports directly demonstrating that Bach-1 activity is altered in EC cultured under FSS, it is of note that disruption of Bach-1 in apoE knockout mice has been reported to inhibit oxidative stress and atherogenesis through the upregulation of HO-1 in the endothelium. 90 However, it remains to be established whether increased Bach-1 levels or activity in atheroprone regions of disturbed FSS lead to diminished Nrf2/ARE activity and antioxidant gene expression.…”

Section: Hypertensionmentioning

confidence: 99%

Nrf2 as an Endothelial Mechanosensitive Transcription Factor

2016

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“…HO-1 has become an especially interesting target for atheroprotection since the ablation of heme-binding transcription repressor Bach1 in apoE-deficient mice, which leads to the overexpression of HO-1 in endothelium, macrophages, and vascular SMCs, suppresses atherosclerosis in Bach1/ apoE double knockout mice [162]. This effect was abrogated by Sn protoporphyrin, an inhibitor of HO activity [163]. HO-1 induction in LDLR-deficient mice by intraperitoneal injections of hemin (H group) or hemin and desferrioxamine (HD group) led to significantly smaller atherosclerotic lesions in the proximal aorta upon feeding a high-fat diet, whereas the group treated with Sn-protoporphyrin presented larger lesions compared with the control group, which received saline only [164].…”

Section: Heme Oxygenase-1mentioning

confidence: 99%

Enzymatic Targets in Atherosclerosis

Fuior¹,

Trusca²,

Roman³

et al. 2015

J Mol Genet Med

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Atherosclerosis, a prime cause of mortality across the developed societies, was targeted by diverse therapeutic strategies. These evolved in response to the complex etiology and evolution of the disease. Many enzymes are associated with atherosclerosis, either in the main stream of lipid biosynthesis and transport or in the collateral and intertwined pathways of oxidative stress, inflammation, vascular remodeling or chromatin stability and are therefore revised herein. Enzyme exploration led to important developments. At the beginning, there were the statins, derived as inhibitors of hydroxy-methyl-glutaryl CoA (HMG-CoA) reductase, currently used widely to decrease lipid levels. At the other end, the inhibitors of the recently discovered proprotein convertase subtilisin/kexin type 9 (PCSK9) are awaiting the validation in clinical trials with great hopes for the future. In between, one can find some palliatives, as aspirin, an inhibitor of cyclooxygenase (COX), but also many invalidated candidates. Classical pharmacological data and newer approaches, like genetic knockouts in murine atherosclerosis models, are reviewed in order to appreciate the involvement of a particular enzyme in atherogenesis. However, the pursuit of an efficacious drug has been long and, in many cases, disappointing. Conclusions can be drawn from the overview of both successes and failures, in a quest for the best.

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Ablation of the Bach1 Gene Leads to the Suppression of Atherosclerosis in Bach1 and Apolipoprotein E Double Knockout Mice

Cited by 47 publications

References 39 publications

Atherogenesis and iron: from epidemiology to cellular level

Atherogenesis and iron: from epidemiology to cellular level

Nrf2 as an Endothelial Mechanosensitive Transcription Factor

Enzymatic Targets in Atherosclerosis

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