scholarly journals (–)-Epicatechin Alters Reactive Oxygen and Nitrogen Species Production Independent of Mitochondrial Respiration in Human Vascular Endothelial Cells

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Daniel G. Sadler ◽  
Jonathan Barlow ◽  
Richard Draijer ◽  
Helen Jones ◽  
Dick H. J. Thijssen ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Mitochondrial Respiration ◽  
Vascular Endothelial Cells ◽  
Cell Signalling ◽  
Reactive Oxygen ◽  
Vascular Endothelial ◽  
Ros Production ◽  
Vascular Endothelial Dysfunction ◽  
Mitochondrial Superoxide ◽  
No Bioavailability

Introduction. Vascular endothelial dysfunction is characterised by lowered nitric oxide (NO) bioavailability, which may be explained by increased production of reactive oxygen species (ROS), mitochondrial dysfunction, and altered cell signalling. (-)-Epicatechin (EPI) has proven effective in the context of vascular endothelial dysfunction, but the underlying mechanisms associated with EPI’s effects remain unclear. Objective(s). Our aim was to investigate whether EPI impacts reactive oxygen and nitrogen species (RONS) production and mitochondrial function of human vascular endothelial cells (HUVECs). We hypothesised that EPI would attenuate ROS production, increase NO bioavailability, and enhance indices of mitochondrial function. Methods. HUVECs were treated with EPI (0-20 μM) for up to 48 h. Mitochondrial and cellular ROS were measured in the absence and presence of antimycin A (AA), an inhibitor of the mitochondrial electron transport protein complex III, favouring ROS production. Genes associated with mitochondrial remodelling and the antioxidant response were quantified by RT-qPCR. Mitochondrial bioenergetics were assessed by respirometry and signalling responses determined by western blotting. Results. Mitochondrial superoxide production without AA was increased 32% and decreased 53% after 5 and 10 μM EPI treatment vs. CTRL ( P < 0.001 ). With AA, only 10 μM EPI increased mitochondrial superoxide production vs. CTRL (25%, P < 0.001 ). NO bioavailability was increased by 45% with 10 μM EPI vs. CTRL ( P = 0.010 ). However, EPI did not impact mitochondrial respiration. NRF2 mRNA expression was increased 1.5- and 1.6-fold with 5 and 10 μM EPI over 48 h vs. CTRL ( P = 0.015 and P = 0.001 , respectively). Finally, EPI transiently enhanced ERK1/2 phosphorylation (2.9 and 3.2-fold over 15 min and 1 h vs. 0 h, respectively; P = 0.035 and P = 0.011 ). Conclusion(s). EPI dose-dependently alters RONS production of HUVECs but does not impact mitochondrial respiration. The induction of NRF2 mRNA expression with EPI might relate to enhanced ERK1/2 signalling, rather than RONS production. In humans, EPI may improve vascular endothelial dysfunction via alteration of RONS and activation of cell signalling.

scholarly journals (—)-Epicatechin alters reactive oxygen and nitrogen species production independent of mitochondrial respiration in human vascular endothelial cells

2021 ◽  
Author(s):  
Daniel G. Sadler
Keyword(s):  
Endothelial Dysfunction ◽  
Mitochondrial Respiration ◽  
Vascular Endothelial Cells ◽  
Cell Signalling ◽  
Reactive Oxygen ◽  
Vascular Endothelial ◽  
Ros Production ◽  
Vascular Endothelial Dysfunction ◽  
Mitochondrial Superoxide ◽  
No Bioavailability

Introduction: Vascular endothelial dysfunction is characterised by lowered nitric oxide (NO) bioavailability, which may be explained by increased production of reactive oxygen species (ROS), mitochondrial dysfunction and altered cell signalling. (—)-Epicatechin (EPI) has proven effective in the context of vascular endothelial dysfunction, but the underlying mechanisms associated with EPIs effects remain unclear. Objective(s): Our aim was to investigate whether EPI impacts reactive oxygen and nitrogen species (RONS) production and mitochondrial function of human vascular endothelial cells (HUVECs). We hypothesised that EPI would attenuate ROS production, increase NO bioavailability, and enhance indices of mitochondrial function. Methods: HUVECs were treated with EPI (0-20 μM) for up to 48 h. Mitochondrial and cellular ROS were measured in the absence and presence of antimycin A (AA), an inhibitor of the mitochondrial electron transport protein complex III, favouring ROS production. Genes associated with mitochondrial remodelling and the antioxidant response were quantified by RT-qPCR. Mitochondrial bioenergetics were assessed by respirometry and signalling responses determined by western blotting. Results: Mitochondrial superoxide production without AA was increased 32% and decreased 53% after 5 and 10 μM EPI treatment vs. CTRL (P<0.001). With AA, only 10 μM EPI increased mitochondrial superoxide production vs. CTRL (25%, P<0.001). NO bioavailability was increased by 45% with 10 μM EPI vs. CTRL (P=0.010). However, EPI did not impact mitochondrial respiration. NRF2 mRNA expression was increased 1.5- and 1.6-fold with 5 and 10 μM EPI over 48 h vs. CTRL (P=0.015 and P=0.001, respectively). Finally, EPI transiently enhanced ERK1/2 phosphorylation (2.9 and 3.2-fold over 15 min and 1 h vs. 0 h, respectively; P=0.035 and P=0.011). Conclusion(s): EPI dose dependently alters RONS production of HUVECs but does not impact mitochondrial respiration. The induction of NRF2 mRNA expression with EPI might relate to enhanced ERK1/2 signalling, rather than RONS production. In humans, EPI may improve vascular endothelial dysfunction via alteration of RONS and activation of cell signalling.

scholarly journals Sinapine Thiocyanate Ameliorates Vascular Endothelial Dysfunction in Hypertension by Inhibiting Activation of the NLRP3 Inflammasome

2021 ◽  
Vol 11 ◽  
Author(s):  
Yang Liu ◽  
Hong-lin Yin ◽  
Chao Li ◽  
Feng Jiang ◽  
Shi-jun Zhang ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Vascular Endothelial Cells ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Inflammasome Activation ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Nlrp3 Gene ◽  
Spontaneously Hypertensive

The increase of blood pressure is accompanied by the changes in the morphology and function of vascular endothelial cells. Vascular endothelial injury and hypertension actually interact as both cause and effect. A large number of studies have proved that inflammation plays a significant role in the occurrence and development of hypertension, but the potential mechanism between inflammation and hypertensive endothelial injury is still ambiguous. The purpose of this study was to explore the association between the activation of NLRP3 inflammasome and hypertensive endothelial damage, and to demonstrate the protective effect of sinapine thiocyanate (ST) on endothelia in hypertension. The expression of NLRP3 gene was silenced by tail vein injection of adeno-associated virus (AAVs) in spontaneously hypertensive rats (SHRs), indicating that activation of NLRP3 inflammasome accelerated hypertensive endothelial injury. ST not only protected vascular endothelial function in SHRs by inhibiting the activation of NLRP3 inflammasome and the expression of related inflammatory mediators, but also improved AngII-induced huvec injury. In summary, our results show that alleviative NLRP3 inflammasome activation attenuates hypertensive endothelial damage and ST ameliorates vascular endothelial dysfunction in hypertension via inhibiting activation of the NLRP3 inflammasome.

Abstract 3684: Short-term Caloric Restriction Reverses Age-associated Vascular Endothelial Dysfunction in Older Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Catarina Rippe ◽  
Melanie L Connell ◽  
Lisa A Lesniewski ◽  
Anthony J Donato ◽  
Douglas R Seals
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Caloric Restriction ◽  
Ex Vivo ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Short Term ◽  
No Bioavailability ◽  
Physiological Benefits

Backgound: Oxidative stress-mediated, nitric oxide (NO)-dependent vascular endothelial dysfunction develops with aging, increasing the risk of cardiovascular diseases. As such, it is important to identify interventions that can prevent/restore the loss of endothelial function with aging. Caloric restriction (CR) is associated with several physiological benefits and increased longevity in rodents. Some of these benefits are linked to increases in SIRT-1, an enzyme activating endothelial NO synthase (eNOS), and reductions in oxidative stress. We tested the hypothesis that short-term CR would restore vascular endothelial function by improving NO bioavailability and reducing oxidative stress in old B6D2F1-mice, and that this would be associated with increased expression of SIRT-1 and eNOS. Methods: Old (30 months) male B6D2F1-mice were either fed ad libitum (AL, n=6) or were restricted to 70% (3.2g) of their normal food intake for 6 weeks after 2 weeks of progressive restriction (n=6). Carotid artery dilation was assessed ex vivo in response to the endothelium-dependent dilator acetylcholine (ACh) [before and after incubation with the eNOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) or the superoxide dismutase mimetic, TEMPOL] and the endothelium-independent dilator sodium nitroprusside (SNP). Results: ACh-induced dilation was markedly impaired in the AL mice, but was completely restored in the CR mice (63±10% vs. 98±1%, P<0.01). L-NAME decreased ACh dilation by 97% in CR, but only 56% in AL mice, indicating increased NO bioavailability in the CR mice. TEMPOL restored ACh-mediated dilation in AL mice (to 97±1%), but had no effect in CR mice. Aortic protein expression of SIRT-1 and eNOS (western blotting) were 80 –90% higher in CR vs. AL mice (eNOS: 1.9±0.1 vs. 1.0±0.4 P<0.05; SIRT-1: 1.8±0.2 vs. 1.0±0.2, P=0.05). Dilation to SNP was similar in the CR and AL mice (97±1% vs. 96±2%, P=0.63). Conclusion: Short-term CR selectively restores endothelium-dependent dilation in older B6D2F1-mice by increasing NO bioavailability and reducing oxidative stress. These effects are associated with increased vascular expression of SIRT-1 and eNOS. CR may be an effective intervention for reversing age-associated vascular endothelial dysfunction.

scholarly journals Mechanism of Vascular Endothelial Dysfunction Causing Arteriosclerosis: Vascular Endothelial Glycocalyx

2020 ◽  
Author(s):  
Minako Yamaoka-Tojo
Keyword(s):  
Endothelial Dysfunction ◽  
Vascular Endothelial Cells ◽  
Endothelial Glycocalyx ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Microvascular Angina ◽  
Coronary Syndrome ◽  
Acute Infectious Disease ◽  
Matrix Bound ◽  
Cell Lining

In atherosclerosis patients, vascular endothelial dysfunction is commonly observed with damage of vascular endothelial glycocalyx, an extracellular matrix-bound to and encapsulating the endothelial cell lining the blood vessel wall. Unfavorable lifestyle; smoking and physical inactivity, also induces glycocalyx degradation. Moreover, the vascular endothelial glycocalyx is damaged by various unfavorable disease conditions like as dehydration, acute infectious disease, trauma, sepsis, ARDS, Kawasaki disease, preeclampsia, gestational diabetes mellitus, hypertension, diabetes, chronic kidney disease, atherosclerosis, stroke, dementia, microvascular angina, acute coronary syndrome, and heart failure. The vascular endothelial glycocalyx has been shown to be important not only as a physical cytoprotective barrier for vascular endothelial cells but also as a mechanism that regulates intracellular cell signaling. Therefore, vascular endothelial glycocalyx has great potential to explore new strategies for assessing the benefit conditions of our healthy vasculature.

Mitochondrial reactive oxygen species-mediated signaling in endothelial cells

2007 ◽  
Vol 292 (5) ◽  
pp. H2023-H2031 ◽  
Author(s):  
David X. Zhang ◽  
David D. Gutterman
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Cell Signaling ◽  
Vascular Endothelial Cells ◽  
Reactive Oxygen ◽  
Vascular Endothelial ◽  
Ros Production ◽  
Oxygen Species ◽  
Mitochondrial Ros

Once thought of as toxic by-products of cellular metabolism, reactive oxygen species (ROS) have been implicated in a large variety of cell-signaling processes. Several enzymatic systems contribute to ROS production in vascular endothelial cells, including NA(D)PH oxidase, xanthine oxidase, uncoupled endothelial nitric oxide synthase, and the mitochondrial electron transport chain. The respiratory chain is the major source of ROS in most mammalian cells, but the role of mitochondria-derived ROS in vascular cell signaling has received little attention. A new paradigm has evolved in recent years postulating that, in addition to producing ATP, mitochondria also play a key role in cell signaling and regulate a variety of cellular functions. This review focuses on the emerging role of mitochondrial ROS as signaling molecules in vascular endothelial cells. Specifically, we discuss some recent findings that indicate that mitochondrial ROS regulate vascular endothelial function, focusing on major sites of ROS production in endothelial mitochondria, factors modulating mitochondrial ROS production, the physiological and clinical implications of endothelial mitochondrial ROS, and methodological considerations in the study of mitochondrial contribution to vascular ROS generation.

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