Low Serum Glutathione Peroxidase Activity Is Associated with Increased Cardiovascular Mortality in Individuals with Low HDLc’s

Buijsse, Brian; Lee, Dong Hoon; Steffen, Lyn M.; Erickson, Richard R.; Luepker, Russell V.; Jacobs, David R.; Holtzman, Jordan L.

doi:10.1371/journal.pone.0038901

Cited by 52 publications

(38 citation statements)

References 25 publications

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“…It has been shown that HO-1 gene transfer inhibits atherosclerosis in apoliporotein E-deficient (ApoE K/K ) mice as well as graft arteriosclerosis and vascular remodeling in rat arteries (Juan et al 2001, Bouchet et al 2002. Apart from HO-1, other Nrf2 downstream targets, such as NQO1, GPx, and Prx I, appear to be involved in the reduction of oxidative damage in the endothelium or arteries during the atheroprotective process (Buijsse et al 2012). Taken together, these data indicate that Nrf2 is an important component in protecting against the pathogenesis of atherosclerosis.…”

Section: Nrf2 and Atherosclerosismentioning

confidence: 99%

The role of Nrf2 in oxidative stress-induced endothelial injuries

Chen¹,

Lu²,

Chen³

et al. 2015

Journal of Endocrinology

335

244

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Endothelial dysfunction is an important risk factor for cardiovascular disease, and it represents the initial step in the pathogenesis of atherosclerosis. Failure to protect against oxidative stress-induced cellular damage accounts for endothelial dysfunction in the majority of pathophysiological conditions. Numerous antioxidant pathways are involved in cellular redox homeostasis, among which the nuclear factor-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway is perhaps the most prominent. Nrf2, a transcription factor with a high sensitivity to oxidative stress, binds to AREs in the nucleus and promotes the transcription of a wide variety of antioxidant genes. Nrf2 is located in the cytoskeleton, adjacent to Keap1. Keap1 acts as an adapter for cullin 3/ring-box 1-mediated ubiquitination and degradation of Nrf2, which decreases the activity of Nrf2 under physiological conditions. Oxidative stress causes Nrf2 to dissociate from Keap1 and to subsequently translocate into the nucleus, which results in its binding to ARE and the transcription of downstream target genes. Experimental evidence has established that Nrf2-driven free radical detoxification pathways are important endogenous homeostatic mechanisms that are associated with vasoprotection in the setting of aging, atherosclerosis, hypertension, ischemia, and cardiovascular diseases. The aim of the present review is to briefly summarize the mechanisms that regulate the Nrf2/Keap1-ARE signaling pathway and the latest advances in understanding how Nrf2 protects against oxidative stress-induced endothelial injuries. Further studies regarding the precise mechanisms by which Nrf2-regulated endothelial protection occurs are necessary for determining whether Nrf2 can serve as a therapeutic target in the treatment of cardiovascular diseases.

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Section: Nrf2 and Atherosclerosismentioning

confidence: 99%

The role of Nrf2 in oxidative stress-induced endothelial injuries

Chen¹,

Lu²,

Chen³

et al. 2015

Journal of Endocrinology

335

244

View full text Add to dashboard Cite

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“…In adolescents, low serum glutathione was an independent risk factor for parental coronary heart disease risk [45]. Moreover, low GPx levels, for which glutathione is a cofactor, combined with low high-density lipoprotein levels may be partly responsible for increased atherosclerosis-related mortality rates in humans [46]. Nrf2 was identified as an important regulator of GPx in mice [47], and therefore taken together, these data demonstrate that Nrf2 is an important component in protection against the pathogenesis of atherosclerosis.…”

Section: Nrf2 As An Antiatherogenic Factormentioning

confidence: 99%

Nrf2and Cardiovascular Defense

Howden

2013

Oxidative Medicine and Cellular Longevity

140

109

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The cardiovascular system is susceptible to a group of diseases that are responsible for a larger proportion of morbidity and mortality than any other disease. Many cardiovascular diseases are associated with a failure of defenses against oxidative stress-induced cellular damage and/or death, leading to organ dysfunction. The pleiotropic transcription factor, nuclear factor-erythroid (NF-E) 2-related factor 2 (Nrf2), regulates the expression of antioxidant enzymes and proteins through the antioxidant response element. Nrf2 is an important component in antioxidant defenses in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Nrf2 is also involved in protection against oxidant stress during the processes of ischemia-reperfusion injury and aging. However, evidence suggests that Nrf2 activity does not always lead to a positive outcome and may accelerate the pathogenesis of some cardiovascular diseases (e.g., atherosclerosis). The precise conditions under which Nrf2 acts to attenuate or stimulate cardiovascular disease processes are unclear. Further studies on the cellular environments related to cardiovascular diseases that influence Nrf2 pathways are required before Nrf2 can be considered a therapeutic target for the treatment of cardiovascular diseases.

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“…GPx deficient mice display an increased level of oxidised LDL and foam cell formation in arteries [8]. Furthermore, a reduced GPx activity is associated with an increased risk of CVD in humans [9,10]. The promotion of GSH synthesis should therefore increase GPx activity and reduce the levels of oxidised lipids and associated CVD risk.…”

Section: Introductionmentioning

confidence: 99%