scholarly journals Sirtuin 1 in Endothelial Dysfunction and Cardiovascular Aging

2021 ◽  
Vol 12 ◽  
Author(s):  
Stefano Ministrini ◽  
Yustina M. Puspitasari ◽  
Georgia Beer ◽  
Luca Liberale ◽  
Fabrizio Montecucco ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Animal Models ◽  
Nicotinamide Adenine Dinucleotide ◽  
Sirtuin 1 ◽  
Future Research ◽  
Metabolic Functions ◽  
Potential Mediator ◽  
Age Related ◽  
The Family

Sirtuin 1 (SIRT1) is a histone deacetylase belonging to the family of Sirtuins, a class of nicotinamide adenine dinucleotide (NAD+)-dependent enzymes with multiple metabolic functions. SIRT1 localizes in the nucleus and cytoplasm, and is implicated in the regulation of cell survival in response to several stimuli, including metabolic ones. The expression of SIRT1 is associated with lifespan and is reduced with aging both in animal models and in humans, where the lack of SIRT1 is regarded as a potential mediator of age-related cardiovascular diseases. In this review, we will summarize the extensive evidence linking SIRT1 functional and quantitative defects to cellular senescence and aging, with particular regard to their role in determining endothelial dysfunction and consequent cardiovascular diseases. Ultimately, we outline the translational perspectives for this topic, in order to highlight the missing evidence and the future research steps.

scholarly journals Regulation of miRNAs by Natural Antioxidants in Cardiovascular Diseases: Focus on SIRT1 and eNOS

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 377
Author(s):  
Yunna Lee ◽  
Eunok Im
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Natural Antioxidants ◽  
Sirtuin 1 ◽  
Potential Benefits ◽  
New Perspective ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Cardiovascular diseases (CVDs) are the most common cause of morbidity and mortality worldwide. The potential benefits of natural antioxidants derived from supplemental nutrients against CVDs are well known. Remarkably, natural antioxidants exert cardioprotective effects by reducing oxidative stress, increasing vasodilation, and normalizing endothelial dysfunction. Recently, considerable evidence has highlighted an important role played by the synergistic interaction between endothelial nitric oxide synthase (eNOS) and sirtuin 1 (SIRT1) in the maintenance of endothelial function. To provide a new perspective on the role of natural antioxidants against CVDs, we focused on microRNAs (miRNAs), which are important posttranscriptional modulators in human diseases. Several miRNAs are regulated via the consumption of natural antioxidants and are related to the regulation of oxidative stress by targeting eNOS and/or SIRT1. In this review, we have discussed the specific molecular regulation of eNOS/SIRT1-related endothelial dysfunction and its contribution to CVD pathologies; furthermore, we selected nine different miRNAs that target the expression of eNOS and SIRT1 in CVDs. Additionally, we have summarized the alteration of miRNA expression and regulation of activities of miRNA through natural antioxidant consumption.

scholarly journals Minireview: NAD+, a Circadian Metabolite with an Epigenetic Twist

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Paolo Sassone-Corsi
Keyword(s):  
Circadian Clock ◽  
Nicotinamide Adenine Dinucleotide ◽  
Mammalian Cells ◽  
Feedback Loop ◽  
Large Fraction ◽  
Sirtuin 1 ◽  
Nicotinamide Adenine ◽  
Dynamic Changes ◽  
Metabolic Functions ◽  
Transcriptional Feedback

Abstract A wide variety of endocrine, physiological, and metabolic functions follow daily oscillations. Most of these regulations are controlled at the level of gene expression by the circadian clock and, a remarkably coordinated transcription-translation machinery that exerts its function in virtually all mammalian cells. A large fraction of the genome is under control of the circadian clock, a regulation that is achieved through dynamic changes in chromatin states. Recent findings have demonstrated intimate connections between the circadian clock and epigenetic control. The case of nicotinamide adenine dinucleotide, which modulates the circadian activity of the deacetylase sirtuin 1, constitutes a paradigmatic example of the link between cyclic cellular metabolism and chromatin remodeling. Indeed, the clock transcriptional feedback loop is interlocked with the enzymatic loop of the nicotinamide adenine dinucleotide salvage pathway.

scholarly journals Trimethylamine-N-Oxide Promotes Age-Related Vascular Oxidative Stress and Endothelial Dysfunction in Mice and Healthy Humans

Hypertension ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 101-112 ◽  
Author(s):  
Vienna E. Brunt ◽  
Rachel A. Gioscia-Ryan ◽  
Abigail G. Casso ◽  
Nicholas S. VanDongen ◽  
Brian P. Ziemba ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Nitric Oxide Synthase ◽  
Flow Mediated Dilation ◽  
Middle Aged ◽  
Healthy Humans ◽  
Age Related ◽  
Oxide Synthase

Age-related vascular endothelial dysfunction is a major antecedent to cardiovascular diseases. We investigated whether increased circulating levels of the gut microbiome-generated metabolite trimethylamine-N-oxide induces endothelial dysfunction with aging. In healthy humans, plasma trimethylamine-N-oxide was higher in middle-aged/older (64±7 years) versus young (22±2 years) adults (6.5±0.7 versus 1.6±0.2 µmol/L) and inversely related to brachial artery flow-mediated dilation ( r 2 =0.29, P <0.00001). In young mice, 6 months of dietary supplementation with trimethylamine-N-oxide induced an aging-like impairment in carotid artery endothelium-dependent dilation to acetylcholine versus control feeding (peak dilation: 79±3% versus 95±3%, P <0.01). This impairment was accompanied by increased vascular nitrotyrosine, a marker of oxidative stress, and reversed by the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl. Trimethylamine-N-oxide supplementation also reduced activation of endothelial nitric oxide synthase and impaired nitric oxide-mediated dilation, as assessed with the nitric oxide synthase inhibitor L-NAME (N G -nitro-L-arginine methyl ester). Acute incubation of carotid arteries with trimethylamine-N-oxide recapitulated these events. Next, treatment with 3,3-dimethyl-1-butanol for 8 to 10 weeks to suppress trimethylamine-N-oxide selectively improved endothelium-dependent dilation in old mice to young levels (peak: 90±2%) by normalizing vascular superoxide production, restoring nitric oxide-mediated dilation, and ameliorating superoxide-related suppression of endothelium-dependent dilation. Lastly, among healthy middle-aged/older adults, higher plasma trimethylamine-N-oxide was associated with greater nitrotyrosine abundance in biopsied endothelial cells, and infusion of the antioxidant ascorbic acid restored flow-mediated dilation to young levels, indicating tonic oxidative stress-related suppression of endothelial function with higher circulating trimethylamine-N-oxide. Using multiple experimental approaches in mice and humans, we demonstrate a clear role of trimethylamine-N-oxide in promoting age-related endothelial dysfunction via oxidative stress, which may have implications for prevention of cardiovascular diseases.

Endothelial Dysfunction: Implications for Therapy of Cardiovascular Diseases

1998 ◽  
Vol 32 (4) ◽  
pp. 459-470 ◽  
Author(s):  
Dawn M Bell ◽  
Thomas E Johns ◽  
Larry M Lopez
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Basic Science ◽  
Lipid Lowering ◽  
Future Research ◽  
Vascular Relaxation ◽  
Dysfonction Endothéliale

OBJECTIVE: To review current literature regarding endothelial dysfunction in cardiovascular diseases and examine implications of these findings for the treatment of various cardiovascular disorders. DATA SOURCE: A MEDLINE search of basic science articles pertinent to understanding the role of the endothelium in the atherosclerotic process and of clinical trials examining the presence and treatment of impaired endothelium-dependent vascular relaxation was conducted. STUDY SELECTION: Selected basic science articles and reviews were included to explain the foundation for subsequent clinical trials. All clinical trials examining the treatment of impaired endothelium-dependent vascular relaxation were reviewed. DATA SYNTHESIS: Endothelial dysfunction characterized by impaired endothelium-dependent vascular relaxation is an early physiologic event in atherogenesis. Endothelial dysfunction in peripheral vasculature serves as a marker for impairment in coronary arteries. Techniques for measuring endothelium-dependent vascular relaxation are specific and have a high positive predictive value for coronary artery disease, but low sensitivity. Various pharmacologic agents have been used in an attempt to improve endothelial function, but only lipid-lowering agents and estrogen supplementation have been shown to improve endothelium-dependent vascular relaxation consistently. Treatments used in patients with heart failure or hypertension fail to demonstrate consistent improvement. CONCLUSIONS: Endothelial dysfunction serves as a marker for cardiovascular disease, but pharmacologic treatment does not consistently restore normal endothelial function. Nevertheless, some of these agents are known to have positive clinical outcomes. Future research using these techniques will provide greater insight into the effects of many commonly used therapies for cardiovascular disease on the pathobiology of endothelial dysfunction. OBJETIVO: Revisar la literatura actual sobre la disfunción endotelial en enfermedades cardiovasculares y las implicaciones de estos hallazgos en el tratamiento de desórdenes cardiovasculares. FUENTES DE INFORMACION: A través de MEDLINE se realizó una búsqueda de artículos científicos relacionados al rol del endotelio en el proceso de aterosclerosis. En la búsqueda también se identificaron estudios clínicos sobre la detección y el tratamiento de disfunción en la relajación vascular dependiente del endotelio. SELECCIÓN DE FUENTES DE INFORMACIÓN: Se seleccionaron artículos de ciencias básicas y resúmenes de estudios para explicar la base de los estudios clínicos. Se revisaron todos los artículos de estudios clínicos que evaluaban el tratamiento de disfunción en la relajación vascular dependiente del endotelio. SÍNTESIS: La disfunción endotelial, caracterizada por una disfunción en la relajación vascular dependiente del endotelio, es un evento fisiológico que ocurre temprano en el proceso de aterogénesis. La disfunción del endotelio de la vasculatura periferal es un indicador de disfunción de las arterias coronarias. Las técnieas para medir la relajación vascular dependiente del endotelio son específicas y tienen un valor predictivo alto para enfermedad de las arterias coronarias pero una baja sensitividad. Se han utilizado varios agentes farmacológicos para tratar de mejorar la función endotelial, pero sólo los agentes antilipidémicos y el reemplazo de estrógenos han sido consecuentes en demostrar una mejoría en la relajación de la vasculatura dependiente de endotelio. Los tratamientos utilizados en los pacientes con fallo cardíaco e hipertensión no han sido consecuentes en demostrar una mejoría. CONCLUSIONES: La disfunción endotelial es un indicador de enfermedad cardiovascular. Aunque algunos agentes han demostrado obtener resultados clínicos positivos, el tratamiento farmacológico no ha sido consecuente en restaurar la función normal del endotelio. Existe la necesidad de realizar estudios clínicos que midan la relajación vascular que depende del endotelio. Estos podrán proveer mayor información sobre los efectos del tratamiento de enfermedades cardiovasculares en la disfunción del endotelio. OBJECTIF: Décrire les implications cliniques possibles de différents traitements pharmacologiques au niveau de la dysfunction endothéliale notée chez une population atteint d'ischémie myocardique, d'hyperlipidémie, d'hypertension, ou d'insuffisance cardiaque congestive. SOURCE: Les articles de science fondamentale examinant le róle de l'endothélium dans le processus athérosclérotique et les études cliniques évaluant l'effet de différents traitements phamacologiques pour rétablir à la normale la fonction endothéliale ont été identifiés et analysés. RÉSUMÉ: La dysfonction endothéliale caractérisée par un phénomène anormal de la relaxation vasculaire est un évènement physiologique précoce de l'athérogenèse. Ses principales manifestations sont en autre une concentration inadéquate soit du facteur de relaxation de l'endothélium, soit de l'oxide nitrique qui agit à titre de puissant vasodilatateur et d'inhibiteur de l'aggrégation plaquettaire, de la prolifération de cellules musculaires lisses, et de l'adhésion des monocytes. Plusieurs recherches ont démontré qu'une dysfonction endothéliale périphérique (telle que mesurée au niveau de l'artère brachiale) représente un marqueur d'une dysfonction endothéliale au niveau coronaire. La valeur prédictive de la dilatation brachiale pour estimer la dilatation coronaire est d'environ 95% bien que celle-ci ait une faible sensitivité. De tous les agents pharmacologiques testés, seuls les agents hypolipémiants et les suppléments d'oestrogènes semblent pouvoir améliorer la fonction endothéliale. Tous les autres traitements utilisés chez les patients hypertendus ou les insuffisants cardiaques n'ont pu démontrer à ce jour des résultats consistants. CONCLUSIONS: Plusieurs études préliminaires concluent qu'une dysfonction endothéliale périphérique constitue un marqueur pour les maladies cardiovasculaires. À ce jour, aucune thérapie ne semble pouvoir restorer cette fonction d'une façon non équivoque. Ce nouveau champ de recherche cardiovasculaire permettra possiblement d'établir un lien éventuel entre les effets endothéliaux et les effets bénéfiques cliniques des différents traitements pharmacologiques utilisés dans le domaine cardiovasculaire.

scholarly journals Therapeutic Potential of Quercetin to Alleviate Endothelial Dysfunction in Age-Related Cardiovascular Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Olina Dagher ◽  
Pauline Mury ◽  
Nathalie Thorin-Trescases ◽  
Pierre Emmanuel Noly ◽  
Eric Thorin ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Therapeutic Potential ◽  
Scientific Evidence ◽  
Epidemiological Studies ◽  
Food Sources ◽  
Physically Active ◽  
Mesenchymal Transition ◽  
Age Related ◽  
Wide Range

The vascular endothelium occupies a catalog of functions that contribute to the homeostasis of the cardiovascular system. It is a physically active barrier between circulating blood and tissue, a regulator of the vascular tone, a biochemical processor and a modulator of coagulation, inflammation, and immunity. Given these essential roles, it comes to no surprise that endothelial dysfunction is prodromal to chronic age-related diseases of the heart and arteries, globally termed cardiovascular diseases (CVD). An example would be ischemic heart disease (IHD), which is the main cause of death from CVD. We have made phenomenal advances in treating CVD, but the aging endothelium, as it senesces, always seems to out-run the benefits of medical and surgical therapies. Remarkably, many epidemiological studies have detected a correlation between a flavonoid-rich diet and a lower incidence of mortality from CVD. Quercetin, a member of the flavonoid class, is a natural compound ubiquitously found in various food sources such as fruits, vegetables, seeds, nuts, and wine. It has been reported to have a wide range of health promoting effects and has gained significant attention over the years. A growing body of evidence suggests quercetin could lower the risk of IHD by mitigating endothelial dysfunction and its risk factors, such as hypertension, atherosclerosis, accumulation of senescent endothelial cells, and endothelial-mesenchymal transition (EndoMT). In this review, we will explore these pathophysiological cascades and their interrelation with endothelial dysfunction. We will then present the scientific evidence to quercetin's anti-atherosclerotic, anti-hypertensive, senolytic, and anti-EndoMT effects. Finally, we will discuss the prospect for its clinical use in alleviating myocardial ischemic injuries in IHD.

scholarly journals Vascular Aging across the Menopause Transition in Healthy Women

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Kerrie L. Moreau ◽  
Kerry L. Hildreth
Keyword(s):  
Endothelial Dysfunction ◽  
Postmenopausal Women ◽  
Endurance Exercise ◽  
Ovarian Function ◽  
Future Research ◽  
Large Artery ◽  
Vascular Aging ◽  
Age Related ◽  
Artery Stiffness ◽  
Menopause Transition

Vascular aging, featuring endothelial dysfunction and large artery stiffening, is a major risk factor for developing cardiovascular disease (CVD). In women, vascular aging appears to be accelerated during the menopause transition, particularly around the late perimenopausal period, presumably related to declines in ovarian function and estrogen levels. The mechanisms underlying endothelial dysfunction and large artery stiffening with the menopause transition are not completely understood. Oxidative stress and the proinflammatory cytokine tumor necrosis factor-α contribute to endothelial dysfunction and large artery stiffening in estrogen-deficient postmenopausal women. Habitual endurance exercise attenuates the age-related increase in large artery stiffness in estrogen-deficient postmenopausal women and can reverse arterial stiffening to premenopausal levels in estrogen-replete postmenopausal women. In contrast, estrogen status appears to play a key permissive role in the adaptive response of the endothelium to habitual endurance exercise in that endothelial improvements are absent in estrogen-deficient women but present in estrogen-replete women. We review here the current state of knowledge on the biological defects underlying vascular aging across the menopause transition, with particular focus on potential mechanisms, the role of habitual exercise in preserving vascular health, and key areas for future research.

scholarly journals Adipose Tissue-Endothelial Cell Interactions in Obesity-Induced Endothelial Dysfunction

2021 ◽  
Vol 8 ◽  
Author(s):  
Manna Li ◽  
Ming Qian ◽  
Kathy Kyler ◽  
Jian Xu
Keyword(s):  
Cardiovascular Disease ◽  
Adipose Tissue ◽  
Endothelial Cell ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Cardiovascular System ◽  
Vascular Injury ◽  
Future Research ◽  
Strong Impact ◽  
Excess Adiposity

Obesity has a strong impact on the pathogenesis of cardiovascular disease, which raises enthusiasm to understand how excess adiposity causes vascular injury. Adipose tissue is an essential regulator of cardiovascular system through its endocrine and paracrine bioactive products. Obesity induces endothelial dysfunction, which often precedes and leads to the development of cardiovascular diseases. Connecting adipose tissue-endothelial cell interplay to endothelial dysfunction may help us to better understand obesity-induced cardiovascular disease. This Mini Review discussed (1) the general interactions and obesity-induced endothelial dysfunction, (2) potential targets, and (3) the outstanding questions for future research.

Risk predictors of arterial hypertension development in population of Mountain Shoriya of various ethnical origins

2019 ◽  
Vol 1 (3) ◽  
pp. 39-42
Author(s):  
T. A. Mulerova ◽  
M. Yu. Ogarkov ◽  
O. L. Barbarash
Keyword(s):  
Cardiovascular Diseases ◽  
Total Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density Lipoprotein Cholesterol ◽  
Type Settlement ◽  
The Family ◽  
Genotype C ◽  
Hypertension Development ◽  
Risk Predictors

1409 people (901 Shors, 508 non-indigenous people) from remote villages of Mountain Shoriya (Orton and Ust-Kabyrsa) and urban-type settlement Sheregesh took part in the survey. In Shors, the risk of developing hypertension was determined by elevated levels of total cholesterol and low density lipoprotein cholesterol, violation of carbohydrate metabolism, obesity, including its abdominal type, the family anamnesis of early cardiovascular diseases, and a carriage of prognostically unfavorable genotypes D/D and C/C of the corresponding genes ACE and AGTR 1 candidates; in the cohort of non-indigenous ethnos-elevated levels of total cholesterol and triglycerides, obesity, abdominal obesity, the family anamnesis of early cardiovascular diseases, a carrier of the minor genotype C/C of the AGTR 1 gene

Information Practices of Baby Boomers as Caregivers

2013 ◽  
Author(s):  
Khuan Seow ◽  
Nadia Caidi
Keyword(s):  
Social Policy ◽  
Baby Boomers ◽  
Information Needs ◽  
Family Members ◽  
Age Groups ◽  
Maladie D’Alzheimer ◽  
Policy Makers ◽  
Age Related ◽  
The Family ◽  
Growing Age

Canada has an aging population with the fastest growing age groups (80 and 45-64 years old) vulnerable to age-related diseases such as Alzheimer’s disease. Caregiving responsibilities often fall to the family members of the afflicted without much attention and consideration being placed on the information needs of these caregivers. We call for a better understanding of these caregivers' information needs and uses by social policy makers as well as information providers.La population du Canada a tendance à vieillir considérablement, avec la hausse la plus rapide dans les groupes d’âge (80 et 45 à 64 ans). Les personnes âges sont très vulnérables à toute sorte de maladies, telles que la maladie d’Alzheimer. La responsabilité revient souvent aux membres de la famille qui doivent prendre soin des personnes atteintes de cette maladie. Or, nous ne connaissons que peu de chose sur les besoins en information des personnes qui prennent soin de ces malades de l’Alzheimer : qui sont-ils ? Quelles sont leurs sources... 

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