2013
DOI: 10.18632/aging.100569
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Abstract: Age-associated decline in cardiovascular function is believed to occur from the deleterious effects of reactive oxygen species (ROS). However, failure of recent clinical trials using antioxidants in patients with cardiovascular disease, and the recent findings showing paradoxical role for NADPH oxidase-derived ROS in endothelial function challenge this long-held notion against ROS. Here, we examine the effects of endothelium-specific conditional increase in ROS on coronary endothelial function. We have generat… Show more

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Cited by 66 publications
(101 citation statements)
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References 51 publications
(96 reference statements)
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“…In certain cells, increased ROS production could result in AMPK activation. Indeed, specific NOX2 overexpression in endothelial cells activates AMPK, inducing NO synthase activation (37). Similarly, in H9C2 cardiomyoblasts, mitochondrial ROS generation in response to nitrite exposure also activates AMPK (21).…”
Section: Discussionmentioning
confidence: 99%
“…In certain cells, increased ROS production could result in AMPK activation. Indeed, specific NOX2 overexpression in endothelial cells activates AMPK, inducing NO synthase activation (37). Similarly, in H9C2 cardiomyoblasts, mitochondrial ROS generation in response to nitrite exposure also activates AMPK (21).…”
Section: Discussionmentioning
confidence: 99%
“…57 The dual function of 2-AG should be taken into account, especially considering that platelet hyperactivation is related to aging, inflammation and cancer. 58,59 Age-related decline in cardiovascular function (and, therefore, susceptibility to thrombotic and inflammatory disorders) is often associated to increased levels of reactive oxygen species and oxidative stress; 60,61 since aged platelets display increased NADPH oxidase expression and hydrogen peroxide generation, platelet hyperactivity may contribute to this phenomenon. 62 Aging and activated platelets also modulate lineage-specific development, as well as the senescence program itself, thus promoting cell transformation and playing a role in the early progression to malignancy; [63][64][65][66] in particular, by shedding micro-RNA-containing microvesicles, activated platelets may have clinical relevance in promoting tumor growth and spread, 67 and potentially could be used as biomarkers, as circulating micro-RNA-containing microvesicles may differ according to cancer stage.…”
Section: Discussionmentioning
confidence: 99%
“…Indeed, downregulation of Nox activity by cytosolic p47phox knockdown or inhibition of Nox2 attenuated the coronary vasodilation to vascular endothelial growth factor (VEGF) [52] and bradykinin [32], respectively. In addition, Nox2 overexpression enhanced the coronary vasodilation in response to both VEGF and acetylcholine [53], further confirming that the vasodilator ROS is derived from Nox in this process. More importantly, Larsen and colleagues proposed that Nox2 is a functionally relevant source of H 2 O 2 that mediates agonist-induced coronary vasodilation [32].…”
Section: Adenosine-induced Increase In Coronary Flow Is Mediated In Pmentioning
confidence: 56%
“…This heterogeneity might be due to vasoconstrictor ROS vs. vasodilator ROS [29,31] generated from different vascular beds (coronary vs. renal artery) [34,37]. Furthermore, in the coronary vasculature, the varying effects of ROS may depend on which source ROS are generated from (NADPH vs. uncoupled NO synthase) [31,52,53] or the pathophysiological conditions [32,52,53], e.g., diabetes, and the right ventricular hypertrophy [54][55][56]. In accordance with our previous studies [37], the effect of ROS scavenging with EUK134 was comparable with the effect of Nox2 inhibition with gp91 ds-tat in WT isolated hearts (P=0.24), suggesting that the majority of ROS generated by adenosine is likely from Nox2, which leads to increases in coronary flow.…”
Section: Adenosine-induced Increase In Coronary Flow Is Mediated In Pmentioning
confidence: 99%