Nrf2-Mediated Dichotomy in the Vascular System: Mechanistic and Therapeutic Perspective

Wu, Weiwei; Hendrix, Andrew; Nair, Sharad; Cui, Taixing

doi:10.3390/cells11193042

Cited by 14 publications

(7 citation statements)

References 199 publications

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“…Nrf2 is thus a critical regulator of cardiovascular homeostasis with implications for the development of cardiovascular disease. For additional readings on this topic, refer to da Costa et al (2019) [ 152 ], Gutiérrez [ 153 ]-Cuevas et al (2022), and Wu et al (2022) [ 154 ].…”

Section: Nrf2 In Human Diseasementioning

confidence: 99%

“…Most cancers show elevated levels of ROS and oxidative stress, which can cause DNA damage, impair protein function, and alter mechanisms of cellular proliferation to promote tumorigenesis [ 154 ]. This is particularly true for cancers of the skin and lung, as both organs are directly exposed to additional sources of environmental ROS which contribute to cancer initiation and aggravation [ 158 , 159 ].…”

Section: Nrf2 In Human Diseasementioning

confidence: 99%

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Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease

2022

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Organisms are continually exposed to exogenous and endogenous sources of reactive oxygen species (ROS) and other oxidants that have both beneficial and deleterious effects on the cell. ROS have important roles in a wide range of physiological processes; however, high ROS levels are associated with oxidative stress and disease progression. Oxidative stress has been implicated in nearly all major human diseases, from neurogenerative diseases and neuropsychiatric disorders to cardiovascular disease, diabetes, and cancer. Antioxidant defence systems have evolved as a means of protection against oxidative stress, with the transcription factor Nrf2 as the key regulator. Nrf2 is responsible for regulating an extensive panel of antioxidant enzymes involved in the detoxification and elimination of oxidative stress and has been extensively studied in the disease contexts. This review aims to provide the reader with a general overview of oxidative stress and Nrf2, including basic mechanisms of Nrf2 activation and regulation, and implications in various major human diseases.

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Section: Nrf2 In Human Diseasementioning

confidence: 99%

Section: Nrf2 In Human Diseasementioning

confidence: 99%

Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease

2022

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“…Furthermore, not all actions of Nrf2 are good for the body. Nrf2 may promote tumours [ 135 , 136 ] and atherogenesis [ 137 , 138 ], so any drug acting on Nrf2 must avoid these two and maybe other unknown potentially harmful actions.…”

Section: Discussionmentioning

confidence: 99%

The Nrf2 Pathway in Depressive Disorders: A Systematic Review of Animal and Human Studies

et al. 2023

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There is increasing interest in the involvement of antioxidative systems in protecting from depression. Among these, Nrf2 occupies a central place. We aimed to review the role of Nrf2 in depression. For this reason, we conducted a PubMed search using as search strategy (psychiatr*[ti] OR schizo*[ti] OR psychot*[ti] OR psychos*[ti] OR depress*[ti] OR MDD[ti] OR BD[ti] OR bipolar[ti] OR Anxiety[ti] OR antidepress*[ti] OR panic[ti] OR obsess*[ti] OR compulsio*[ti] OR “mood disord*”[ti] OR phobi*[ti] OR agoraphob*[ti] OR anorex*[ti] OR anorect*[ti] OR bulimi*[ti] OR “eating disorder*”[ti] OR neurodevelopm*[ti] OR retardation[ti] OR autism[ti] OR autistic[ti] OR ASM[ti] OR adhd[ti] OR “attention-deficit”[ti]) AND nrf2, which on the 9th of March produced 208 results of which 89 were eligible for our purposes. Eligible articles were studies reporting data of Nrf2 manipulations or content by any treatment in human patients or animals with any animal model of depression. Most studies were on mice only (N = 58), 20 on rats only, and three on both rats and mice. There were two studies on cell lines (in vitro) and one each on nematodes and fish. Only four studies were conducted in humans, one of which was post mortem. Most studies were conducted on male animals; however, human studies were carried out on both men and women. The results indicate that Nrf2 is lower in depression and that antidepressant methods (drugs or other methods) increase it. Antioxidant systems and plasticity-promoting molecules, such as those in the Nrf2–HO-1, BDNF–TrkB, and cyclic AMP–CREB pathways, could protect from depression, while glycogen synthase kinase-3β and nuclear factor κB oppose these actions, thus increasing depressive-like behaviours. Since Nrf2 is also endowed with tumorigenic and atherogenic potential, the balance between benefits and harms must be taken into account in designing novel drugs aiming at increasing the intracellular content of Nrf2.

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“…Aging and Disease • Volume 15, Number 5, October 2024 NQO1, heme oxygenase-1 (HO-1) and ferritin, to maintain redox homeostasis [68]. Stimulation of Nrf2 can have positive effects on the endothelium and powerful anti-inflammatory and pro-angiogenic effects on the developing vascular system [69][70][71]. Compelling evidence supports the theory that Nrf2 dysfunction in the aging vascular system worsens oxidative stress and reduces the ability of vascular cells to withstand ROSmediated cytotoxicity.…”

Section: Irisin Promotes Healthy Vascular Agingmentioning

confidence: 97%

Irisin: A Potentially Fresh Insight into the Molecular Mechanisms Underlying Vascular Aging

Wang,

Wang

2023

Aging and disease

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Aging is a natural process that affects all living organisms, including humans. Aging is a complex process that involves the gradual deterioration of various biological processes and systems, including the cardiovascular system. Vascular aging refers to age-related changes in blood vessels. These changes can increase the risk of developing cardiovascular diseases, such as hypertension, atherosclerosis, and stroke. Recently, an exercise-induced muscle factor, irisin, was found to directly improve metabolism and regulate the balance of glucolipid metabolism, thereby counteracting obesity and insulin resistance. Based on a growing body of evidence, irisin modulates vascular aging. Adenosine monophosphate-activated protein kinase (AMPK) serves as a pivotal cellular energy sensor and metabolic modulator, acting as a central signaling cascade to coordinate various cellular processes necessary for maintaining vascular homeostasis. The vascular regulatory effects of irisin are closely intertwined with its interaction with the AMPK pathway. In conclusion, understanding the molecular processes used by irisin to regulate changes in vascular diseases caused by aging may inspire the development of techniques that promote healthy vascular aging. This review sought to describe the impact of irisin on the molecular mechanisms of vascular aging, including inflammation, oxidative stress, and epigenetics, from the perspective of endothelial cell function and vascular macroregulation, and summarize the multiple signaling pathways used by irisin to regulate vascular aging.

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Nrf2-Mediated Dichotomy in the Vascular System: Mechanistic and Therapeutic Perspective

Cited by 14 publications

References 199 publications

Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease

Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease

The Nrf2 Pathway in Depressive Disorders: A Systematic Review of Animal and Human Studies

Irisin: A Potentially Fresh Insight into the Molecular Mechanisms Underlying Vascular Aging

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