Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases

Incalza, Maria Angela; D’Oria, Rossella; Natalicchio, Annalisa; Perrini, Sebastio; Laviola, Luigi

doi:10.1016/j.vph.2017.05.005

Cited by 945 publications

(802 citation statements)

References 267 publications

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“…It is important to note, however, that oxidative stress has been postulated as a potential culprit responsible for instigating endothelial activation. Thus, in the case of SSc, it remains unclear if oxidative stress leads to inflammation, or if inflammation leads to oxidative stress (Fuschiotti, 2016; Gabrielli et al, 2012; Incalza et al, 2017; Matucci-Cerinic et al, 2013). However, while the seminal event remains elusive, it is evident that both inflammation and oxidative stress contribute significantly to the progression of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…In SSc, an initial vascular insult leads to endothelial cell activation and the initiation of pro-inflammatory cascades, as well as a vicious cycle of chronic ischemia and intermittent reperfusion that results in deleterious histological changes and the generation of an excess of free radicals and reactive oxygen species (ROS) (Fuschiotti, 2016; Gabrielli, Svegliati, Moroncini, & Amico, 2012). When the generation of ROS outstrips the body’s antioxidant capacity, this leads to a state of “oxidative stress” and can cause oxidative damage to cells, as well as to lipids, carbohydrates, and proteins (Incalza et al, 2017). ROS also attenuate the bioavailability of nitric oxide (NO), a potent endogenous vasodilator, thus, potentially, further impacting vascular function in this patient group.…”

Section: Introductionmentioning

confidence: 99%

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Attenuated nitric oxide bioavailability in systemic sclerosis: Evidence from the novel assessment of passive leg movement

Clifton

Machin

Groot

et al. 2018

Experimental Physiology

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Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, which may be the consequence of inflammation and oxidative stress that ultimately leads to a reduced nitric oxide (NO) bioavailability. Passive leg movement (PLM) is a novel methodology for assessing lower limb vascular function that is predominantly NO dependent. We combined this vascular assessment with a comprehensive panel of plasma biomarkers to assess the axis of inflammation, oxidative stress and NO in SSc patients (n = 12; 62 ± 11 years of age) compared with healthy control subjects (n = 17; 60 ± 16 years of age). The PLM-induced changes in leg blood flow (LBF; 191 ± 104 versus 327 ± 217 ml min ) and LBF area under the curve (39 ± 104 versus 125 ± 131 ml) were reduced in SSc compared with control subjects. Stratification of patients according to history of digital ulcer (DU) formation revealed a further reduction in LBF area under the curve in DU (-13 ± 83 ml) versus non-DU (91 ± 102 ml) patients. Biomarkers of inflammation (C-reactive protein) and oxidative stress (malondialdehyde and protein carbonyl) were all elevated in SSc (C-reactive protein, 3299 ± 2372 versus 984 ± 565 ng ml ; malondialdehyde, 3.2 ± 1.1 versus 1.1 ± 0.7 μm; and protein carbonyl, 0.15 ± 0.05 versus 0.12 ± 0.03 nmol mg ), and C-reactive protein was further elevated in patients with a history of DU (4551 ± 2752 versus 2047 ± 1019 ng ml ) compared with non-DU, although these were not individually correlated with changes in LBF. These findings of impaired NO-mediated vascular function, linked to DU and a milieu of inflammation and oxidative stress, suggest that redox balance plays an important, but not necessarily deterministic, role in the vascular pathophysiology of SSc.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Attenuated nitric oxide bioavailability in systemic sclerosis: Evidence from the novel assessment of passive leg movement

Clifton

Machin

Groot

et al. 2018

Experimental Physiology

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“…It is well known that the oxidative stress which is induced by overproduction of ROS causes endothelial dysfunction and cellular injury, and promotes the development of atherosclerosis and other cardiovascular disease (7, 37). The underlying mechanism is that oxidative stress triggers apoptosis in endothelial cells, alters the integrity of the endothelium, and initiates the formation of atherosclerotic plaques (38,39).…”

Section: Discussionmentioning

confidence: 99%

Lunasin attenuates oxidant‐induced endothelial injury and inhibits atherosclerotic plaque progression in ApoE^−/−mice by up‐regulating heme oxygenase‐1viaPI3K/Akt/Nrf2/ARE pathway

et al. 2019

FASEB j.

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Oxidative stress–induced vascular endothelial cell (VEC) injury is a major mechanism in the initiation and development of atherosclerosis. Lunasin, a soybean‐derived 43‐aa peptide, has been previously shown to possess potent antioxidant and anti‐inflammatory activities other than its established anticancer activities. This study investigated the effects of lunasin on protecting VECs from oxidative damage and inhibiting atherosclerotic plaque progression in apolipoprotein E–deficient (ApoE−/−) mice and explored its underlying mechanism. Biochemical and histologic analyses were performed by using EA.hy926 human VECs and a high‐fat diet (HFD) ApoE−/− mouse atherosclerosis model. Our data indicated that lunasin attenuated H2O2‐induced, mitochondria‐dependent endothelial apoptosis via down‐regulating Bax and up‐regulating Bcl‐2, inhibiting the mitochondrial depolarization, and reducing the release of cytochrome c, as well as decreasing the activation of casρase‐9 and caspase‐3 in vitro and in vivo. Mechanic studies showed that lunasin significantly up‐regulated heme oxygenase‐1 via the PI3K/Akt/nuclear factor erythroid 2–related factor 2/antioxidant response element pathway, and reduced H2O2‐induced ROS production in VECs, thereby attenuating oxidant‐induced endothelial injury and inhibiting atherosclerotic plaque progression in ApoE−/− mice. In conclusion, our in vitro and in vivo data suggest that lunasin protects VECs from oxidative damage by enhancing heme oxygenase‐1 expression via activation of the PI3K/Akt/ nuclear factor erythroid 2–related factor 2/antioxidant response element pathway and inhibiting mitochondria‐dependent apoptosis, thereby effectively attenuating atherosclerosis in HFD‐fed ApoE−/− mice. Lunasin may act as a potential therapeutic agent for the prevention and treatment of atherosclerosis.—Gu, L., Ye, P., Li, H., Wang, Y., Xu, Y., Tian, Q., Lei, G., Zhao, C., Gao, Z., Zhao, W., Tan, S. Lunasin attenuates oxidant‐induced endothelial injury and inhibits atherosclerotic plaque progression in ApoE−/− mice by up‐regulating heme oxygenase‐1 via PI3K/Akt/ Nrf2/ARE pathway. FASEB J. 33, 4836–4850 (2019). http://www.fasebj.org

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“…Oxidative stress from inflammation may cause endothelial cells to increase production of the vasoconstrictive protein endothelin‐1 . Further, NO may be consumed as it reacts with oxidants, thereby limiting the bioavailability for vascular function . Decreased endothelial‐derived vasodilatory signals can inappropriately diminish perfusion to a specific tissue.…”

Section: Perturbationsmentioning

confidence: 99%

Developmental onset of cardiovascular disease—Could the proof be in the placenta?

D’Errico

Stapleton

2019

Microcirculation

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The Barker Hypothesis states change to the maternal environment may have significant impacts on fetal development, setting the stage for adult disease to occur. The development of the materno-fetal vasculature during implantation and maintenance during pregnancy is extremely precise, yet dynamic. Delays or dysfunction in the orchestration of anatomical remodeling, maintenance of blood pressure, or responsiveness to metabolic demand may have severe consequences to the developing fetus. While these intermissions may not be fatal to the developing fetus, an interruption, reduction, or an inability to meet fetal demand of blood flow during crucial stages of development may pre-dispose young to disease later in life. Maternal inability to meet fetal demand can be attributed to improper placental development and vascular support through morphological change or physiological function will significantly limit nutrient delivery and waste exchange to the developing fetus. Therefore, we present an overview of the uteroplacental vascular network, maternal cardiovascular adaptations that occur during pregnancy, placental blood flow, and common maternal comorbidities and/or exposures that may perturb maternal homeostasis and affect fetal development. Overall, we examine uterine microvasculature pathophysiology contributing to a hostile gestational environment and fetal predisposition to disease as it relates to the Barker Hypothesis.

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Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases

Cited by 945 publications

References 267 publications

Attenuated nitric oxide bioavailability in systemic sclerosis: Evidence from the novel assessment of passive leg movement

Attenuated nitric oxide bioavailability in systemic sclerosis: Evidence from the novel assessment of passive leg movement

Lunasin attenuates oxidant‐induced endothelial injury and inhibits atherosclerotic plaque progression in ApoE^−/−mice by up‐regulating heme oxygenase‐1viaPI3K/Akt/Nrf2/ARE pathway

Developmental onset of cardiovascular disease—Could the proof be in the placenta?

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Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases

Cited by 945 publications

References 267 publications

Attenuated nitric oxide bioavailability in systemic sclerosis: Evidence from the novel assessment of passive leg movement

Attenuated nitric oxide bioavailability in systemic sclerosis: Evidence from the novel assessment of passive leg movement

Lunasin attenuates oxidant‐induced endothelial injury and inhibits atherosclerotic plaque progression in ApoE−/−mice by up‐regulating heme oxygenase‐1viaPI3K/Akt/Nrf2/ARE pathway

Developmental onset of cardiovascular disease—Could the proof be in the placenta?

Contact Info

Product

Resources

About

Lunasin attenuates oxidant‐induced endothelial injury and inhibits atherosclerotic plaque progression in ApoE^−/−mice by up‐regulating heme oxygenase‐1viaPI3K/Akt/Nrf2/ARE pathway