Protective effect of extracellular superoxide dismutase on endothelial function during aging

Lund, Donald D.; Chu, Yi; Miller, Jordan D.; Heistad, Donald D.

doi:10.1152/ajpheart.01342.2008

Cited by 52 publications

(43 citation statements)

References 29 publications

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“…In ecSOD knockout mice, lack of ecSOD has no significant effect on blood pressure under normal physiological conditions; however, lack of ecSOD augments angiotensin II (AII)-induced hypertension and promotes endothelial dysfunction. Endothelial dysfunction, characterized by a lack of dilation of blood vessels in response to endothelium-dependent vasoactive substances, such as acetylcholine, is consistent with a deficiency of bioavailable NO (158,200,266). Recent findings indicate that extracellular alterations in redox potential promote alterations in intracellular redox balance that affect mitochondrial production of ROS (155,184).…”

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confidence: 99%

Redox Regulation of Mitochondrial Function

Handy

Loscalzo

2012

Antioxidants & Redox Signaling

482

334

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Redox-dependent processes influence most cellular functions, such as differentiation, proliferation, and apoptosis. Mitochondria are at the center of these processes, as mitochondria both generate reactive oxygen species (ROS) that drive redox-sensitive events and respond to ROS-mediated changes in the cellular redox state. In this review, we examine the regulation of cellular ROS, their modes of production and removal, and the redoxsensitive targets that are modified by their flux. In particular, we focus on the actions of redox-sensitive targets that alter mitochondrial function and the role of these redox modifications on metabolism, mitochondrial biogenesis, receptor-mediated signaling, and apoptotic pathways. We also consider the role of mitochondria in modulating these pathways, and discuss how redox-dependent events may contribute to pathobiology by altering mitochondrial function. Antioxid. Redox Signal. 16, 1323-1367.

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mentioning

confidence: 99%

Redox Regulation of Mitochondrial Function

Handy

Loscalzo

2012

Antioxidants & Redox Signaling

482

334

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“…Previous work in aged humans and animals has shown that NAD(P)H oxidase contributes to age-related endothelial dysfunction and vascular fibrosis and that reducing SOD1 (cytosolic), SOD2 (mitochondrial), or SOD3 (extracellular) worsens endothelial function with aging (3,4,12,13,19,25). Furthermore, we have previously shown that aortic valve calcification is strongly associated with increases in oxidative stress and reductions in antioxidant defense mechanisms in humans (27), and several studies have shown that the balance between oxidative stress and nitric oxide bioavailability is an important determinant of vascular and valvular calcification in vitro (27,39,41).…”

mentioning

confidence: 99%

Transcriptional and phenotypic changes in aorta and aortic valve with aging and MnSOD deficiency in mice

Roos

Hagler

Zhang

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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-The purpose of this study was to characterize changes in antioxidant and age-related gene expression in aorta and aortic valve with aging, and test the hypothesis that increased mitochondrial oxidative stress accelerates age-related endothelial and aortic valve dysfunction. Wildtype (MnSOD ϩ/ϩ ) and manganese SOD heterozygous haploinsufficient (MnSOD ϩ/Ϫ ) mice were studied at 3 and 18 mo of age. In aorta from wild-type mice, antioxidant expression was preserved, although there were age-associated increases in Nox2 expression. Haploinsufficiency of MnSOD did not alter antioxidant expression in aorta, but increased expression of Nox2. When compared with that of aorta, age-associated reductions in antioxidant expression were larger in aortic valves from wild-type and MnSOD haploinsufficient mice, although Nox2 expression was unchanged. Similarly, sirtuin expression was relatively well-preserved in aorta from both genotypes, whereas expression of SIRT1, SIRT2, SIRT3, SIRT4, and SIRT6 were significantly reduced in the aortic valve. Expression of p16 ink4a , a marker of cellular senescence, was profoundly increased in both aorta and aortic valve from MnSOD ϩ/ϩ and MnSOD ϩ/Ϫ mice. Functionally, we observed comparable age-associated reductions in endothelial function in aorta from both MnSOD ϩ/ϩ and MnSOD ϩ/Ϫ mice. Interestingly, inhibition of NAD(P)H oxidase with apocynin or gp91ds-tat improved endothelial function in MnSOD ϩ/ϩ mice but significantly impaired endothelial function in MnSOD ϩ/Ϫ mice at both ages. Aortic valve function was not impaired by aging or MnSOD haploinsufficiency. Changes in antioxidant and sirtuin gene expression with aging differ dramatically between aorta and aortic valve. Furthermore, although MnSOD does not result in overt cardiovascular dysfunction with aging, compensatory transcriptional responses to MnSOD deficiency appear to be tissue specific.aging; mitochondrial oxidative stress; endothelial function; aorta; aortic valve INCREASING AGE IS ASSOCIATED with increases in reactive oxygen species (ROS), which is thought to contribute to the development of age-related cardiovascular disease. Previous work in aged humans and animals has shown that NAD(P)H oxidase contributes to age-related endothelial dysfunction and vascular fibrosis and that reducing SOD1 (cytosolic), SOD2 (mitochondrial), or SOD3 (extracellular) worsens endothelial function with aging (3,4,12,13,19,25). Furthermore, we have previously shown that aortic valve calcification is strongly associated with increases in oxidative stress and reductions in antioxidant defense mechanisms in humans (27), and several studies have shown that the balance between oxidative stress and nitric oxide bioavailability is an important determinant of vascular and valvular calcification in vitro (27,39,41). Interestingly, emerging data from in vitro experiments also suggest that, once initiated, ROS production may self-perpetuate (ROS-induced ROS-release), accelerate development of endothelial dysfunction, and accelerate development of age-relate...

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“…The third SOD isoform present in the extracellular vasculature, SOD3, protects vascular cells from superoxide-inactivation of endothelial cellular signal NO; SOD3 expression was reported to decrease in aged mice (106). As ROS levels increase in aged tissues, antioxidant machinery becomes even more imperative to manage oxidative stress.…”

Section: Cellular Anti-oxidant Machinerymentioning

confidence: 99%

Nicotinamide Riboside Delivery Generates Nad+ Reserves to Protect Vascular Cells Against Oxidative Damage

Hawrylyshyn¹,

Yin²,

O’Neil³

et al. 2015

Canadian Journal of Cardiology

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Protective effect of extracellular superoxide dismutase on endothelial function during aging

Abstract: Lund DD, Chu Y, Miller JD, Heistad DD. Protective effect of extracellular superoxide dismutase on endothelial function during aging.

Cited by 52 publications

References 29 publications

Redox Regulation of Mitochondrial Function

Redox Regulation of Mitochondrial Function

Transcriptional and phenotypic changes in aorta and aortic valve with aging and MnSOD deficiency in mice

Nicotinamide Riboside Delivery Generates Nad+ Reserves to Protect Vascular Cells Against Oxidative Damage

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