Antioxidants

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23 pages, 3164 KiB

Open AccessArticle

Contribution of Mitochondrial Reactive Oxygen Species to Chronic Hypoxia-Induced Pulmonary Hypertension

by Simin Yan, Joshua R. Sheak, Benjimen R. Walker, Nikki L. Jernigan and Thomas C. Resta

Antioxidants 2023, 12(12), 2060; https://doi.org/10.3390/antiox12122060 - 30 Nov 2023

Cited by 3 | Viewed by 2310

Abstract

Pulmonary hypertension (PH) resulting from chronic hypoxia (CH) occurs in patients with chronic obstructive pulmonary diseases, sleep apnea, and restrictive lung diseases, as well as in residents at high altitude. Previous studies from our group and others demonstrate a detrimental role of reactive [...] Read more.

Pulmonary hypertension (PH) resulting from chronic hypoxia (CH) occurs in patients with chronic obstructive pulmonary diseases, sleep apnea, and restrictive lung diseases, as well as in residents at high altitude. Previous studies from our group and others demonstrate a detrimental role of reactive oxygen species (ROS) in the pathogenesis of CH-induced PH, although the subcellular sources of ROS are not fully understood. We hypothesized that mitochondria-derived ROS (mtROS) contribute to enhanced vasoconstrictor reactivity and PH following CH. To test the hypothesis, we exposed rats to 4 weeks of hypobaric hypoxia (P_B ≈ 380 mmHg), with control rats housed in ambient air (P_B ≈ 630 mmHg). Chronic oral administration of the mitochondria-targeted antioxidant MitoQ attenuated CH-induced decreases in pulmonary artery (PA) acceleration time, increases in right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary arterial remodeling. In addition, endothelium-intact PAs from CH rats exhibited a significantly greater basal tone compared to those from control animals, as was eliminated via MitoQ. CH also augmented the basal tone in endothelium-disrupted PAs, a response associated with increased mtROS production in primary PA smooth muscle cells (PASMCs) from CH rats. However, we further uncovered an effect of NO synthase inhibition with Nω–nitro-L-arginine (L-NNA) to unmask a potent endothelial vasoconstrictor influence that accentuates mtROS-dependent vasoconstriction following CH. This basal tone augmentation in the presence of L-NNA disappeared following combined endothelin A and B receptor blockade with BQ123 and BQ788. The effects of using CH to augment vasoconstriction and PASMC mtROS production in exogenous endothelin 1 (ET-1) were similarly prevented by MitoQ. We conclude that mtROS participate in the development of CH-induced PH. Furthermore, mtROS signaling in PASMCs is centrally involved in enhanced pulmonary arterial constriction following CH, a response potentiated by endogenous ET-1. Full article

(This article belongs to the Special Issue Oxidative Stress in Vascular Regulation, Disease and Treatment)

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28 pages, 6151 KiB

Open AccessArticle

Sepsis-Induced Coagulopathy Phenotype Induced by Oxidized High-Density Lipoprotein Associated with Increased Mortality in Septic-Shock Patients

by Yolanda Prado, Pablo Tapia, Felipe Eltit, Cristian Reyes-Martínez, Carmen G. Feijóo, Felipe M. Llancalahuen, Claudia A. Riedel, Claudio Cabello-Verrugio, Jimmy Stehberg and Felipe Simon

Antioxidants 2023, 12(3), 543; https://doi.org/10.3390/antiox12030543 - 21 Feb 2023

Cited by 4 | Viewed by 2584

Abstract

Sepsis syndrome is a highly lethal uncontrolled response to an infection, which is characterized by sepsis-induced coagulopathy (SIC). High-density lipoprotein (HDL) exhibits antithrombotic activity, regulating coagulation in vascular endothelial cells. Sepsis induces the release of several proinflammatory molecules, including reactive oxygen species, which [...] Read more.

Sepsis syndrome is a highly lethal uncontrolled response to an infection, which is characterized by sepsis-induced coagulopathy (SIC). High-density lipoprotein (HDL) exhibits antithrombotic activity, regulating coagulation in vascular endothelial cells. Sepsis induces the release of several proinflammatory molecules, including reactive oxygen species, which lead to an increase in oxidative stress in blood vessels. Thus, circulating lipoproteins, such as HDL, are oxidized to oxHDL, which promotes hemostatic dysfunction, acquiring prothrombotic properties linked to the severity of organ failure in septic-shock patients (SSP). However, a rigorous and comprehensive investigation demonstrating that oxHDL is associated with a coagulopathy-associated deleterious outcome of SSP, has not been reported. Thus, we investigated the participation of plasma oxHDL in coagulopathy-associated sepsis pathogenesis and elucidated the underlying molecular mechanism. A prospective study was conducted on 42 patients admitted to intensive care units, (26 SSP and 16 non-SSP) and 39 healthy volunteers. We found that an increased plasma oxHDL level in SSP was associated with a prothrombotic phenotype, increased mortality and elevated risk of death, which predicts mortality in SSP. The underlying mechanism indicates that oxHDL triggers an endothelial protein expression reprogramming of coagulation factors and procoagulant adhesion proteins, to produce a prothrombotic environment, mainly mediated by the endothelial LOX-1 receptor. Our study demonstrates that an increased plasma oxHDL level is associated with coagulopathy in SSP through a mechanism involving the endothelial LOX-1 receptor and endothelial protein expression regulation. Therefore, the plasma oxHDL level plays a role in the molecular mechanism associated with increased mortality in SSP. Full article

(This article belongs to the Special Issue Oxidative Stress in Vascular Regulation, Disease and Treatment)

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15 pages, 3633 KiB

Open AccessArticle

Peroxisome Proliferator-Activated Receptor α Attenuates Hypertensive Vascular Remodeling by Protecting Vascular Smooth Muscle Cells from Angiotensin II-Induced ROS Production

by Ye Liu, Yan Duan, Nan Zhao, Xinxin Zhu, Xiaoting Yu, Shiyu Jiao, Yanting Song, Li Shi, Yutao Ma, Xia Wang, Baoqi Yu and Aijuan Qu

Antioxidants 2022, 11(12), 2378; https://doi.org/10.3390/antiox11122378 - 30 Nov 2022

Cited by 6 | Viewed by 1694

Abstract

Vascular remodeling is the fundamental basis for hypertensive disease, in which vascular smooth muscle cell (VSMC) dysfunction plays an essential role. Previous studies suggest that the activation of peroxisome proliferator-activated receptor α (PPARα) by fibrate drugs has cardiovascular benefits independent of the lipid-lowering [...] Read more.

Vascular remodeling is the fundamental basis for hypertensive disease, in which vascular smooth muscle cell (VSMC) dysfunction plays an essential role. Previous studies suggest that the activation of peroxisome proliferator-activated receptor α (PPARα) by fibrate drugs has cardiovascular benefits independent of the lipid-lowering effects. However, the underlying mechanism remains incompletely understood. This study explored the role of PPARα in angiotensin II (Ang II)-induced vascular remodeling and hypertension using VSMC-specific Ppara-deficient mice. The PPARα expression was markedly downregulated in the VSMCs upon Ang II treatment. A PPARα deficiency in the VSMC significantly aggravated the Ang II-induced hypertension and vascular stiffness, with little influence on the cardiac function. The morphological analyses demonstrated that VSMC-specific Ppara-deficient mice exhibited an aggravated vascular remodeling and oxidative stress. In vitro, a PPARα deficiency dramatically increased the production of mitochondrial reactive oxidative species (ROS) in Ang II-treated primary VSMCs. Finally, the PPARα activation by Wy14643 improved the Ang II-induced ROS production and vascular remodeling in a VSMC PPARα-dependent manner. Taken together, these data suggest that PPARα plays a critical protective role in Ang II-induced hypertension via attenuating ROS production in VSMCs, thus providing a potential therapeutic target for hypertensive diseases. Full article

(This article belongs to the Special Issue Oxidative Stress in Vascular Regulation, Disease and Treatment)

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12 pages, 983 KiB

Open AccessArticle

Natural Activators of Autophagy Increase Maximal Walking Distance and Reduce Oxidative Stress in Patients with Peripheral Artery Disease: A Pilot Study

by Ombretta Martinelli, Mariangela Peruzzi, Simona Bartimoccia, Alessandra D’Amico, Simona Marchitti, Speranza Rubattu, Giovanni Alfonso Chiariello, Luca D’Ambrosio, Sonia Schiavon, Fabio Miraldi, Wael Saade, Mizar D’Abramo, Annachiara Pingitore, Lorenzo Loffredo, Cristina Nocella, Maurizio Forte and Pasquale Pignatelli

Antioxidants 2022, 11(9), 1836; https://doi.org/10.3390/antiox11091836 - 18 Sep 2022

Cited by 6 | Viewed by 5965

Abstract

Trehalose, spermidine, nicotinamide, and polyphenols have been shown to display pro-autophagic and antioxidant properties, eventually reducing cardiovascular and ischemic complications. This study aimed to investigate whether a mixture of these components improves maximal walking distance (MWD) in peripheral artery disease (PAD) patients. Nitrite/nitrate [...] Read more.

Trehalose, spermidine, nicotinamide, and polyphenols have been shown to display pro-autophagic and antioxidant properties, eventually reducing cardiovascular and ischemic complications. This study aimed to investigate whether a mixture of these components improves maximal walking distance (MWD) in peripheral artery disease (PAD) patients. Nitrite/nitrate (NOx), endothelin-1, sNOX2-dp, H₂O₂ production, H₂O₂ break-down activity (HBA), ATG5 and P62 levels, flow-mediated dilation (FMD), and MWD were evaluated in 20 PAD patients randomly allocated to 10.5 g of mixture or no-treatment in a single-blind study. The above variables were assessed at baseline and 60 days after mixture ingestion. Compared with baseline, mixture intake significantly increased MWD (+91%; p < 0.01) and serum NOx (+96%; p < 0.001), whereas it significantly reduced endothelin-1 levels (−30%, p < 0.01). Moreover, mixture intake led to a remarkable reduction in sNOX2dp (−31%, p < 0.05) and H₂O₂ (−40%, p < 0.001) and potentiated antioxidant power (+110%, p < 0.001). Finally, mixture ingestion restored autophagy by increasing ATG5 (+43%, p < 0.01) and decreasing P62 (−29%, p < 0.05). No changes in the above-mentioned variables were observed in the no-treatment group. The treatment with a mixture of trehalose, spermidine, nicotinamide, and polyphenols improves MWD in PAD patients, with a mechanism possibly related to NOX2-mediated oxidative stress downregulation and autophagic flux upregulation. Clinical Trial Registration unique identifier: NCT04061070. Full article

(This article belongs to the Special Issue Oxidative Stress in Vascular Regulation, Disease and Treatment)

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22 pages, 4707 KiB

Open AccessArticle

Muscone and (+)-Borneol Cooperatively Strengthen CREB Induction of Claudin 5 in IL-1β-Induced Endothelium Injury

by Yu-Chen Li, Yi Li, Yu-Ning Zhang, Qiong Zhao, Pei-Lin Zhang, Meng-Ru Sun, Bao-Lin Liu, Hua Yang and Ping Li

Antioxidants 2022, 11(8), 1455; https://doi.org/10.3390/antiox11081455 - 26 Jul 2022

Cited by 9 | Viewed by 2884

Abstract

Claudin 5 is one of the major proteins of tight junctions and is responsible for cerebrovascular integrity and BBB function. Muscone and (+)-borneol is the major ingredient of moschus and borneolum, respectively, with antioxidative and anti-inflammatory activities. This study investigated whether muscone and [...] Read more.

Claudin 5 is one of the major proteins of tight junctions and is responsible for cerebrovascular integrity and BBB function. Muscone and (+)-borneol is the major ingredient of moschus and borneolum, respectively, with antioxidative and anti-inflammatory activities. This study investigated whether muscone and (+)-borneol combination protected claudin 5 by targeting ROS-mediated IL-1β accumulation. Muscone and (+)-borneol reduced cerebral infarct volume and cerebrovascular leakage with claudin 5 protection in mice after stroke, largely due to inhibiting ROS accumulation and inflammatory infiltrate of microglia. Muscone reduced ROS and then blocked the CaN/Erk1/2 pathway to decrease IL-1β release, while (+)-borneol removed mitochondrial ROS and attenuated the SDH/Hif-1α pathway to inhibit IL-1β transcription, thereby jointly reducing IL-1β production. Accumulated IL-1β disrupted cAMP/CREB activation and attenuated transcriptional regulation of claudin 5. Muscone and (+)-borneol combination cooperatively protected BBB function by blocking IL-1β-mediated cAMP/CREB/claudin 5 cascades. Mutation of Ser133 site of CREB or knockdown of claudin 5 weakened the effects of muscone and (+)-borneol on upregulation of TEER value and downregulation of FITC-dextran permeability, suggesting that targeting CREB/claudin 5 was an important strategy to protect vascular integrity. This study provided ideas for the studies of synergistic protection against ischemic brain injury about the active ingredients of traditional Chinese medicines (TCMs). Full article

(This article belongs to the Special Issue Oxidative Stress in Vascular Regulation, Disease and Treatment)

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15 pages, 3561 KiB

Open AccessArticle

Soluble Epoxide Hydrolase Inhibitor t-AUCB Ameliorates Vascular Endothelial Dysfunction by Influencing the NF-κB/miR-155-5p/eNOS/NO/IκB Cycle in Hypertensive Rats

by Xiaorui Wang, Wenwen Han, Yi Zhang, Yi Zong, Na Tan, Yan Zhang, Li Li, Chang Liu and Limei Liu

Antioxidants 2022, 11(7), 1372; https://doi.org/10.3390/antiox11071372 - 15 Jul 2022

Cited by 9 | Viewed by 2013

Abstract

Epoxyeicosatrienoic acids (EETs), angiogenic mediators degraded by soluble epoxide hydrolase (sEH), have been shown to exert beneficial effects on the cardiovascular system. The current study assessed the impact of increased EETs with an sEH inhibitor, t-AUCB, on two-kidney-one-clip (2K1C)-induced renovascular endothelial dysfunction, associated [...] Read more.

Epoxyeicosatrienoic acids (EETs), angiogenic mediators degraded by soluble epoxide hydrolase (sEH), have been shown to exert beneficial effects on the cardiovascular system. The current study assessed the impact of increased EETs with an sEH inhibitor, t-AUCB, on two-kidney-one-clip (2K1C)-induced renovascular endothelial dysfunction, associated with hypertension, in rats. The hypertensive rats exhibited increased systolic blood pressure, reduced renal blood flow, impaired endothelium-dependent relaxation and eNOS phosphorylation in the renal arteries, elevated ROS production in the endothelium of the renal arteries, and decreased EET levels in plasma, the renal arteries, and endothelial cells; however, t-AUCB reversed all the deleterious effects. Moreover, we found that the stimulation of AMPK/UCP2 scavenged ROS and restored endothelial function in the renal arteries of hypertensive rats undergoing therapy with t-AUCB. In addition, we were the first to reveal the potential role of miR-155-5p in the occurrence and development of vascular endothelial dysfunction in hypertension. Importantly, t-AUCB recovered NO bioavailability by regulating the NF-κB/miR-155-5p/eNOS/NO/IκB cycle after the activation of AMPK/UCP2 and the subsequent inhibition of ROS in hypertensive rat renal artery endothelial cells. This study will provide evidence for this additional new mechanism, underlying the benefits of EETs and the related agents against hypertensive vasculopathy. Full article

(This article belongs to the Special Issue Oxidative Stress in Vascular Regulation, Disease and Treatment)

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14 pages, 4143 KiB

Open AccessArticle

Leonurine Attenuates Obesity-Related Vascular Dysfunction and Inflammation

by Xiao-Dong Shi, Jia-Xin Zhang, Xi-De Hu, Tao Zhuang, Ning Lu and Cheng-Chao Ruan

Antioxidants 2022, 11(7), 1338; https://doi.org/10.3390/antiox11071338 - 8 Jul 2022

Cited by 7 | Viewed by 2427

Abstract

Oxidative stress in adipose tissue is a crucial pathogenic mechanism of obesity-associated cardiovascular diseases. Chronic low-grade inflammation caused by obesity increases ROS production and dysregulation of adipocytokines. Leonurine (LEO) is an active alkaloid extracted from Herba Leonuri and plays a protective role in [...] Read more.

Oxidative stress in adipose tissue is a crucial pathogenic mechanism of obesity-associated cardiovascular diseases. Chronic low-grade inflammation caused by obesity increases ROS production and dysregulation of adipocytokines. Leonurine (LEO) is an active alkaloid extracted from Herba Leonuri and plays a protective role in the cardiovascular system. The present study tested whether LEO alleviates inflammation and oxidative stress, and improves vascular function in an obese mouse model. Here, we found that obesity leads to inflammation and oxidative stress in epididymal white adipose tissue (EWAT), as well as vascular dysfunction. LEO significantly improved inflammation and oxidative stress both in vivo and in vitro. Obesity-induced vascular dysfunction was also improved by LEO as evidenced by the ameliorated vascular tone and decreased mesenteric artery fibrosis. Using mass spectrometry, we identified YTHDF1 as the direct target of LEO. Taken together, we demonstrated that LEO improves oxidative stress and vascular remodeling induced by obesity and targets YTHDF1, raising the possibility of LEO treating other obesity-related metabolic syndromes. Full article

(This article belongs to the Special Issue Oxidative Stress in Vascular Regulation, Disease and Treatment)

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15 pages, 3100 KiB

Open AccessArticle

3,4′,5-Trimethoxy-trans-stilbene Alleviates Endothelial Dysfunction in Diabetic and Obese Mice via Activation of the AMPK/SIRT1/eNOS Pathway

by Chunxiu Zhou, Yi Tan, Baojun Xu, Yitao Wang and Wai-San Cheang

Antioxidants 2022, 11(7), 1286; https://doi.org/10.3390/antiox11071286 - 28 Jun 2022

Cited by 9 | Viewed by 2593

Abstract

3,4′,5-trimethoxy-trans-stilbene (TMS) is a methoxylated derivative of resveratrol. Previous studies showed the vaso-protective effects of resveratrol; nevertheless, research on this derivative is scarce. The current study aimed to explore whether TMS can alleviate endothelial dysfunction in diabetic and obese mice, along [...] Read more.

3,4′,5-trimethoxy-trans-stilbene (TMS) is a methoxylated derivative of resveratrol. Previous studies showed the vaso-protective effects of resveratrol; nevertheless, research on this derivative is scarce. The current study aimed to explore whether TMS can alleviate endothelial dysfunction in diabetic and obese mice, along with the underlying mechanisms. Thoracic aortas isolated from male C57BL/6J mice and primary cultures of rat aortic endothelial cells were treated with high glucose with or without TMS. High glucose exposure impaired acetylcholine-induced endothelium-dependent relaxations, down-regulated NO bioavailability and the AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1)/endothelial nitric oxide synthase (eNOS) pathway, increased endoplasmic reticulum (ER) stress and oxidative stress, which were reversed by TMS treatment. Moreover, the protective effects of TMS were abolished by Compound C (AMPK inhibitor), and EX527 (SIRT1 inhibitor). The mice were fed with high-fat diet (60% kcal% fat) for 14 weeks to establish a diabetic and obese model, and were orally administered TMS (10 mg/kg/day) in the last 4 weeks. Chronic TMS treatment alleviated endothelial dysfunction via enhancing the AMPK/SIRT1/eNOS pathway and attenuated oxidative stress and ER stress in aortas of diet-induced obese mice. In summary, our study reveals the potent vaso-protective effect of TMS and its therapeutic potential against endothelial dysfunction in metabolic disorders. Full article

(This article belongs to the Special Issue Oxidative Stress in Vascular Regulation, Disease and Treatment)

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17 pages, 3658 KiB

Open AccessArticle

Activation of AMPK/miR-181b Axis Alleviates Endothelial Dysfunction and Vascular Inflammation in Diabetic Mice

by Chak-Kwong Cheng, Wenbin Shang, Jian Liu, Wai-San Cheang, Yu Wang, Li Xiang, Chi-Wai Lau, Jiang-Yun Luo, Chi-Fai Ng, Yu Huang and Li Wang

Antioxidants 2022, 11(6), 1137; https://doi.org/10.3390/antiox11061137 - 9 Jun 2022

Cited by 25 | Viewed by 3341

Abstract

Hyperglycemia in diabetes mellitus impairs endothelial function and disrupts microRNA (miRNA) profiles in vasculature, increasing the risk of diabetes-associated complications, including coronary artery disease, diabetic retinopathy, and diabetic nephropathy. miR-181b was previously reported to be an anti-inflammatory mediator in vasculature against atherosclerosis. The [...] Read more.

Hyperglycemia in diabetes mellitus impairs endothelial function and disrupts microRNA (miRNA) profiles in vasculature, increasing the risk of diabetes-associated complications, including coronary artery disease, diabetic retinopathy, and diabetic nephropathy. miR-181b was previously reported to be an anti-inflammatory mediator in vasculature against atherosclerosis. The current study aimed to investigate whether miR-181b ameliorates diabetes-associated endothelial dysfunction, and to identify potential molecular mechanisms and upstream inducer of miR-181b. We found that miR-181b level was decreased in renal arteries of diabetic patients and in advanced glycation end products (AGEs)-treated renal arteries of non-diabetic patients. Transfection of miR-181b mimics improved endothelium-dependent vasodilation in aortas of high fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice, accompanied by suppression of superoxide overproduction and vascular inflammation markers. AMPK activator-induced AMPK activation upregulated miR-181b level in human umbilical vein endothelial cells (HUVECs). Chronic exercise, potentially through increased blood flow, activated AMPK/miR-181b axis in aortas of diabetic mice. Exposure to laminar shear stress upregulated miR-181b expression in HUVECs. Overall, our findings highlight a critical role of AMPK/miR-181b axis and extend the benefits of chronic exercise in counteracting diabetes-associated endothelial dysfunction. Full article

(This article belongs to the Special Issue Oxidative Stress in Vascular Regulation, Disease and Treatment)

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16 pages, 4412 KiB

Open AccessArticle

Impact of Selective Renal Afferent Denervation on Oxidative Stress and Vascular Remodeling in Spontaneously Hypertensive Rats

by Lu-Lu Wu, Yue Zhang, Xiu-Zhen Li, Xin-Li Du, Ying Gao, Jing-Xiao Wang, Xiao-Li Wang, Qi Chen, Yue-Hua Li, Guo-Qing Zhu and Xiao Tan

Antioxidants 2022, 11(5), 1003; https://doi.org/10.3390/antiox11051003 - 20 May 2022

Cited by 22 | Viewed by 3139

Abstract

Oxidative stress and sustained sympathetic over-activity contribute to the pathogenesis of hypertension. Catheter-based renal denervation has been used as a strategy for treatment of resistant hypertension, which interrupts both afferent and efferent renal fibers. However, it is unknown whether selective renal afferent denervation [...] Read more.

Oxidative stress and sustained sympathetic over-activity contribute to the pathogenesis of hypertension. Catheter-based renal denervation has been used as a strategy for treatment of resistant hypertension, which interrupts both afferent and efferent renal fibers. However, it is unknown whether selective renal afferent denervation (RAD) may play beneficial roles in attenuating oxidative stress and sympathetic activity in hypertension. This study investigated the impact of selective RAD on hypertension and vascular remodeling. Nine-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were subjected to selective renal afferent denervation (RAD) with 33 mM of capsaicin for 15 min. Treatment with the vehicle of capsaicin was used as a control. The selective denervation was confirmed by the reduced calcitonin gene-related peptide expression and the undamaged renal sympathetic nerve activity response to the stimulation of adipose white tissue. Selective RAD reduced plasma norepinephrine levels, improved heart rate variability (HRV) and attenuated hypertension in SHR.It reduced NADPH oxidase (NOX) expression and activity, and superoxide production in the hypothalamic paraventricular nucleus (PVN), aorta and mesenteric artery of SHR. Moreover, the selective RAD attenuated the vascular remodeling of the aorta and mesenteric artery of SHR. These results indicate that selective removal of renal afferents attenuates sympathetic activity, oxidative stress, vascular remodeling and hypertension in SHR. The attenuated superoxide signaling in the PVN is involved in the attenuation of sympathetic activity in SHR, and the reduced sympathetic activity at least partially contributes to the attenuation of vascular oxidative stress and remodeling in the arteries of hypertensive rats. Full article

(This article belongs to the Special Issue Oxidative Stress in Vascular Regulation, Disease and Treatment)

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15 pages, 3771 KiB

Open AccessArticle

Sirtuin 3 Dependent and Independent Effects of NAD⁺ to Suppress Vascular Inflammation and Improve Endothelial Function in Mice

by Xiaoyun Cao, Yalan Wu, Huiling Hong and Xiao Yu Tian

Antioxidants 2022, 11(4), 706; https://doi.org/10.3390/antiox11040706 - 2 Apr 2022

Cited by 6 | Viewed by 4064

Abstract

Atherosclerosis is initiated by endothelial cell dysfunction and vascular inflammation under the condition of hyperlipidemia. Sirtuin 3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent mitochondrial deacetylase, which plays a key role in maintaining normal mitochondrial function. The present study tested whether [...] Read more.

Atherosclerosis is initiated by endothelial cell dysfunction and vascular inflammation under the condition of hyperlipidemia. Sirtuin 3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent mitochondrial deacetylase, which plays a key role in maintaining normal mitochondrial function. The present study tested whether endothelial-selective SIRT3 deletion accelerates vascular inflammation and oxidative stress, and assessed the protective effect of NAD⁺ to alleviate these changes in endothelial cells and in mouse models of atherosclerosis. We found that the selective deletion of SIRT3 in endothelial cells further impaired endothelium-dependent vasodilatation in the aorta treated with IL-1β, which was accompanied by upregulation of vascular inflammation markers and mitochondrial superoxide overproduction. Excepting the dysfunction of endothelium-dependent vasodilatation, such effects could be attenuated by treatment with NAD⁺. In human umbilical vein endothelial cells, SIRT3 silencing potentiated the induction of inflammatory factors by IL-1β, including VCAM-1, ICAM-1, and MCP1, and the impairment of mitochondrial respiration, both of which were alleviated by NAD⁺ treatment. In ApoE-deficient mice fed with a high-cholesterol diet, supplementation with nicotinamide riboside, the NAD⁺ precursor, reduced plaque formation, improved vascular function, and diminished vascular inflammation. Our results support the SIRT3-dependent and -independent of NAD⁺ to improve endothelial function in atherosclerosis. Full article

(This article belongs to the Special Issue Oxidative Stress in Vascular Regulation, Disease and Treatment)

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Review

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16 pages, 963 KiB

Open AccessReview

NAD⁺ Homeostasis and NAD⁺-Consuming Enzymes: Implications for Vascular Health

by Roberto Campagna and Arianna Vignini

Antioxidants 2023, 12(2), 376; https://doi.org/10.3390/antiox12020376 - 4 Feb 2023

Cited by 36 | Viewed by 3938

Abstract

Nicotinamide adenine dinucleotide (NAD⁺) is a ubiquitous metabolite that takes part in many key redox reactions. NAD⁺ biosynthesis and NAD⁺-consuming enzymes have been attracting markedly increasing interest since they have been demonstrated to be involved in several crucial [...] Read more.

Nicotinamide adenine dinucleotide (NAD⁺) is a ubiquitous metabolite that takes part in many key redox reactions. NAD⁺ biosynthesis and NAD⁺-consuming enzymes have been attracting markedly increasing interest since they have been demonstrated to be involved in several crucial biological pathways, impacting genes transcription, cellular signaling, and cell cycle regulation. As a consequence, many pathological conditions are associated with an impairment of intracellular NAD⁺ levels, directly or indirectly, which include cardiovascular diseases, obesity, neurodegenerative diseases, cancer, and aging. In this review, we describe the general pathways involved in the NAD⁺ biosynthesis starting from the different precursors, analyzing the actual state-of-art of the administration of NAD⁺ precursors or blocking NAD⁺-dependent enzymes as strategies to increase the intracellular NAD⁺ levels or to counteract the decline in NAD⁺ levels associated with ageing. Subsequently, we focus on the disease-related and age-related alterations of NAD⁺ homeostasis and NAD⁺-dependent enzymes in endothelium and the consequent vascular dysfunction, which significantly contributes to a wide group of pathological disorders. Full article

(This article belongs to the Special Issue Oxidative Stress in Vascular Regulation, Disease and Treatment)

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22 pages, 799 KiB

Open AccessReview

Resveratrol in Treating Diabetes and Its Cardiovascular Complications: A Review of Its Mechanisms of Action

by Meiming Su, Wenqi Zhao, Suowen Xu and Jianping Weng

Antioxidants 2022, 11(6), 1085; https://doi.org/10.3390/antiox11061085 - 30 May 2022

Cited by 55 | Viewed by 5466

Abstract

Diabetes mellitus (DM) is one of the most prevalent chronic diseases worldwide. High morbidity and mortality caused by DM are closely linked to its complications in multiple organs/tissues, including cardiovascular complications, diabetic nephropathy, and diabetic neuropathy. Resveratrol is a plant-derived polyphenolic compound with [...] Read more.

Diabetes mellitus (DM) is one of the most prevalent chronic diseases worldwide. High morbidity and mortality caused by DM are closely linked to its complications in multiple organs/tissues, including cardiovascular complications, diabetic nephropathy, and diabetic neuropathy. Resveratrol is a plant-derived polyphenolic compound with pleiotropic protective effects, ranging from antioxidant and anti-inflammatory to hypoglycemic effects. Recent studies strongly suggest that the consumption of resveratrol offers protection against diabetes and its cardiovascular complications. The protective effects of resveratrol involve the regulation of multiple signaling pathways, including inhibition of oxidative stress and inflammation, enhancement of insulin sensitivity, induction of autophagy, regulation of lipid metabolism, promotion of GLUT4 expression, and translocation, and activation of SIRT1/AMPK signaling axis. The cardiovascular protective effects of resveratrol have been recently reviewed in the literature, but the role of resveratrol in preventing diabetes mellitus and its cardiovascular complications has not been systematically reviewed. Therefore, in this review, we summarize the pharmacological effects and mechanisms of action of resveratrol based on in vitro and in vivo studies, highlighting the therapeutic potential of resveratrol in the prevention and treatment of diabetes and its cardiovascular complications. Full article

(This article belongs to the Special Issue Oxidative Stress in Vascular Regulation, Disease and Treatment)

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