Oxidative Stress in Arterial Hypertension (HTN): The Nuclear Factor Erythroid Factor 2-Related Factor 2 (Nrf2) Pathway, Implications and Future Perspectives

Apostol, Alina Georgiana; Costea, Claudia Florida; Tărniceriu, Claudia Cristina; Tudorancea, Ionuț; Mărănducă, Minela Aida; Floria, Mariana; Șerban, Ionela Lăcrămioara

doi:10.3390/pharmaceutics14030534

Cited by 17 publications

(15 citation statements)

References 165 publications

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“…Tanase et al investigated Nrf2 in oxidative stress and its role in AH. Nrf2 is a critical redox-sensitive transcription factor, functioning as a target nuclear receptor against oxidative stress, and it is a major component of the redox homeostasis of cells [ 101 ]. Chronic oxidative stress inhibits Nrf2 activity and function [ 102 ].…”

Section: Arterial Hypertensionmentioning

confidence: 99%

Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

et al. 2022

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Cardiovascular diseases (CVDs) are disorders associated with the heart and circulatory system. Atherosclerosis is its major underlying cause. CVDs are chronic and can remain hidden for a long time. Moreover, CVDs are the leading cause of global morbidity and mortality, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of CVDs, focusing on coronary artery disease along with atherosclerosis as its major cause and arterial hypertension. We discuss the endothelium dysfunction, inflammatory factors, and oxidation associated with atherosclerosis. Mechanisms such as dysfunction of the endothelium and inflammation, which have been identified as critical pathways for development of coronary artery disease, have become easier to diagnose in recent years. Relatively recently, evidence has been found indicating that interactions of the molecular and cellular elements such as matrix metalloproteinases, elements of the immune system, and oxidative stress are involved in the pathophysiology of arterial hypertension. Many studies have revealed several important inflammatory and genetic risk factors associated with CVDs. However, further investigation is crucial to improve our knowledge of CVDs progression and, more importantly, accelerate basic research to improve our understanding of the mechanism of pathophysiology.

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Section: Arterial Hypertensionmentioning

confidence: 99%

Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

et al. 2022

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“…Overproduction of ROS/RNS impairs vascular cell function along with reduced availability and vasoconstriction of NO . , in turn, eliciting HTN ( Griendling et al, 2021 ; Krzemińska et al, 2022 ; Tanase et al, 2022 ). While the precise role of Nrf2 in HTN remains to be established, several associations among Nrf2 and ROS/RNS have been detected in HTN animal models ( Tanase et al, 2022 ).…”

Section: Role Of Nrf2 Signaling In Cvdsmentioning

confidence: 99%

“…, in turn, eliciting HTN ( Griendling et al, 2021 ; Krzemińska et al, 2022 ; Tanase et al, 2022 ). While the precise role of Nrf2 in HTN remains to be established, several associations among Nrf2 and ROS/RNS have been detected in HTN animal models ( Tanase et al, 2022 ). Nrf2 is crucial in the regulation of blood pressure (BP) in multiple ways.…”

Section: Role Of Nrf2 Signaling In Cvdsmentioning

confidence: 99%

“…Similarly, HO-1 expression effectively reverses OS injury in mice with arterial HTN and vascular dysfunction caused by environmental stress, such as noise exposure ( Bayo Jimenez et al, 2021 ). The Nrf2-induced vasoprotective effect on HTN may present another protective mechanism ( Tanase et al, 2022 ). Selective Nrf2 gene deletion in the rostral ventrolateral medulla.…”

Section: Role Of Nrf2 Signaling In Cvdsmentioning

confidence: 99%

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Activation of Nrf2 signaling: A key molecular mechanism of protection against cardiovascular diseases by natural products

Wei

Yang

et al. 2022

Front. Pharmacol.

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Cardiovascular diseases (CVD) are a group of cardiac and vascular disorders including myocardial ischemia, congenital heart disease, heart failure, hypertension, atherosclerosis, peripheral artery disease, rheumatic heart disease, and cardiomyopathies. Despite considerable progress in prophylaxis and treatment options, CVDs remain a leading cause of morbidity and mortality and impose an extremely high socioeconomic burden. Oxidative stress (OS) caused by disequilibrium in the generation of reactive oxygen species plays a crucial role in the pathophysiology of CVDs. Nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor of endogenous antioxidant defense systems against OS, is considered an ideal therapeutic target for management of CVDs. Increasingly, natural products have emerged as a potential source of Nrf2 activators with cardioprotective properties and may therefore provide a novel therapeutic tool for CVD. Here, we present an updated comprehensive summary of naturally occurring products with cardioprotective properties that exert their effects by suppression of OS through activation of Nrf2 signaling, with the aim of providing useful insights for the development of therapeutic strategies exploiting natural products.

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“…This set of genes regulates the expression of phase II detoxifying enzymes, including NAD(P)H: quinone oxidoreductase 1 (NQO1) or glutathione peroxidase (GPx), and antioxidant proteins such as heme oxygenase-1 (HO-1) (Yamamoto et al, 2018;Robledinos-Antón et al, 2019). Nrf2 has been related to different CVDs such as hypertension and atherosclerosis (Alonso-Piñeiro et al, 2021;Tanase et al, 2022). Thus, Nrf2 downregulation in stroke-prone spontaneously hypertensive rats (SHRSP) contributes to the increased oxidative stress and vascular dysfunction observed in this model (Lopes et al, 2015); however, patients who suffer from atherosclerosis have higher levels of Nrf2/HO-1 than healthy subjects (Fiorelli et al, 2019), suggesting that Nrf2 activation is an adaptive mechanism against oxidative stress characteristic of this CVDs.…”

Section: Introductionmentioning

confidence: 99%

Regulation by Nrf2 of IL-1β-induced inflammatory and oxidative response in VSMC and its relationship with TLR4

González-Carnicero

Hernanz²,

Martínez-Casales³

et al. 2023

Front. Pharmacol.

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Introduction: Vascular oxidative stress and inflammation play an important role in the pathogenesis of cardiovascular diseases (CVDs). The proinflammatory cytokine Interleukin-1β (IL-1β) participates in the vascular inflammatory and oxidative responses and influences vascular smooth muscle cells (VSMC) phenotype and function, as well as vascular remodelling in cardiovascular diseases. The Toll-like receptor 4 (TLR4) is also involved in the inflammatory response in cardiovascular diseases. A relationship between Interleukin-1β and Toll-like receptor 4 pathway has been described, although the exact mechanism of this interaction remains still unknown. Moreover, the oxidative stress sensitive transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) promotes the transcription of several antioxidant and anti-inflammatory genes. Nuclear factor-erythroid 2-related factor 2 activators have shown to possess beneficial effects in cardiovascular diseases in which oxidative stress and inflammation are involved, such as hypertension and atherosclerosis; however, the molecular mechanisms are not fully understood. Here, we analysed the role of Toll-like receptor 4 in the oxidative and inflammatory effects of Interleukin-1β as well as whether nuclear factor-erythroid 2-related factor 2 activation contributes to vascular alterations by modulating these effects.Materials: For this purpose, vascular smooth muscle cells and mice aortic segments stimulated with Interleukin-1β were used.Results: Interleukin-1β induces MyD88 expression while the Toll-like receptor 4 inhibitor CLI-095 reduces the Interleukin-1β-elicited COX-2 protein expression, reactive oxygen species (ROS) production, vascular smooth muscle cells migration and endothelial dysfunction. Additionally, Interleukin-1β increases nuclear factor-erythroid 2-related factor 2 nuclear translocation and expression of its downstream proteins heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 and superoxide dismutase-2, by an oxidative stress-dependent mechanism; moreover, Interleukin-1β reduces the expression of the nuclear factor-erythroid 2-related factor 2 inhibitor Keap1. The nuclear factor-erythroid 2-related factor 2 activator tert-butylhydroquinone (tBHQ) reduces the effects of Interleukin-1β on the increased reactive oxygen species production and the expression of the proinflammatory markers (p-p38, p-JNK, p-c-Jun, COX-2), the increased cell proliferation and migration and prevents the Interleukin-1β-induced endothelial dysfunction in mice aortas. Additionally, tert-butylhydroquinone also reduces the increased MyD88 expression, NADPHoxidase activity and cell migration induced by lipopolysaccharide.Conclusions: In summary, this study reveals that Toll-like receptor 4 pathway contributes to the prooxidant and proinflammatory Interleukin-1β-induced effects. Moreover, activation of nuclear factor-erythroid 2-related factor 2 prevents the deleterious effects of Interleukin-1β, likely by reducing Toll-like receptor 4-dependent pathway. Although further research is needed, the results are promising as they suggest that nuclear factor-erythroid 2-related factor 2 activators might protect against the oxidative stress and inflammation characteristic of cardiovascular diseases.

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Oxidative Stress in Arterial Hypertension (HTN): The Nuclear Factor Erythroid Factor 2-Related Factor 2 (Nrf2) Pathway, Implications and Future Perspectives

Cited by 17 publications

References 165 publications

Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

Activation of Nrf2 signaling: A key molecular mechanism of protection against cardiovascular diseases by natural products

Regulation by Nrf2 of IL-1β-induced inflammatory and oxidative response in VSMC and its relationship with TLR4

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