Sirtuin 6 deficiency induces endothelial cell senescence via downregulation of forkhead box M1 expression DOI Creative Commons
Ok-Hee Lee,

Yun Mi Woo,

Sohyeon Moon

et al.

Aging, Journal Year: 2020, Volume and Issue: 12(21), P. 20946 - 20967

Published: Nov. 10, 2020

Cellular senescence of endothelial cells causes vascular dysfunction, promotes atherosclerosis, and contributes to the development age-related diseases. Sirtuin 6 (SIRT6), a conserved NAD+-dependent protein deacetylase, has beneficial effects against aging, despite fact that its functional mechanisms are largely uncharacterized. Here, we show SIRT6 protects from senescence. expression is progressively decreased during both oxidative stress-induced replicative deficiency leads growth arrest, premature Using genetically engineered cell-specific knockout mice, also down-regulation in exacerbates aging. Expression microarray analysis demonstrated modulates multiple genes involved cell cycle regulation. Specifically, appears regulate forkhead box M1 (FOXM1), critical transcription factor for progression Overexpression FOXM1 ameliorates deficiency-induced In this work, demonstrate role as an anti-aging vasculature. These data may provide basis future novel therapeutic approaches disorders.

Language: Английский

Food as medicine: targeting the uraemic phenotype in chronic kidney disease DOI
Denise Mafra, Natália Alvarenga Borges, Bengt Lindholm

et al.

Nature Reviews Nephrology, Journal Year: 2020, Volume and Issue: 17(3), P. 153 - 171

Published: Sept. 22, 2020

Language: Английский

Citations

181
Senescence mechanisms and targets in the heart DOI Open Access
Maggie Chen, Richard Lee, Jessica C. Garbern

et al.

Cardiovascular Research, Journal Year: 2021, Volume and Issue: 118(5), P. 1173 - 1187

Published: May 5, 2021

Abstract Cellular senescence is a state of irreversible cell cycle arrest associated with ageing. Senescence different cardiac types can direct the pathophysiology cardiovascular diseases (CVDs) such as atherosclerosis, myocardial infarction, and fibrosis. While age-related telomere shortening represents major cause replicative senescence, senescent also be induced by oxidative stress, metabolic dysfunction, epigenetic regulation, among other stressors. It critical that we understand molecular pathways lead to cellular consequences in order develop new therapeutic approaches treat CVD. In this review, discuss mechanisms explore how (including cardiomyocytes, endothelial cells, fibroblasts, vascular smooth muscle valve interstitial cells) CVD, highlight potential target prevent or

Language: Английский

Citations

165
Dietary Anti-Aging Polyphenols and Potential Mechanisms DOI Creative Commons
Jing Luo, Hongwei Si, Zhenquan Jia

et al.

Antioxidants, Journal Year: 2021, Volume and Issue: 10(2), P. 283 - 283

Published: Feb. 13, 2021

For years, the consumption of a diet rich in fruits and vegetables has been considered healthy, increasing longevity, decreasing morbidities. With assistance basic research investigating potential mechanisms, it become clear that beneficial effects plant-based foods are mainly due to large amount bioactive phenolic compounds contained. Indeed, substantial dietary intervention studies humans have supported supplementation polyphenols various health-promoting effects, especially elderly population. In vitro examinations on anti-aging mechanisms widely performed, using different types natural synthetic compounds. The aim this review is critically evaluate experimental evidence demonstrating aging-related diseases. We highlight polyphenols, including antioxidant signaling, preventing cellular senescence, targeting microRNA, influencing NO bioavailability, promoting mitochondrial function. While trends utilizing disorders getting growing attention, we suggest exploration combination multiple or polyphenol-rich foods, as would be more physiologically relevant daily life.

Language: Английский

Citations

127
Impact of Lifestyles (Diet and Exercise) on Vascular Health: Oxidative Stress and Endothelial Function DOI Creative Commons
Andy W. C. Man, Huige Li, Ning Xia

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 22

Published: Sept. 26, 2020

Healthy lifestyle and diet are associated with significant reduction in risk of obesity, type 2 diabetes, cardiovascular diseases. Oxidative stress the imbalance between prooxidants antioxidants linked to metabolic Changes antioxidant capacity body may lead oxidative vascular dysfunction. Diet is an important source antioxidants, while exercise offers many health benefits as well. Recent findings have evidenced that physical factors correlated stress. debatable roles modulating effects on endothelium. Since endothelium play critical diseases, dietary could implications prevention This review aimed at summarizing current knowledge impact manipulation stress, focusing We discuss friend-and-foe role modification (including different styles, calorie restriction, nutrient supplementation) well potential concerns activity A fine balance for normal functions cells interfering this unfavorable effects. Further studies needed identify best composition intensity.

Language: Английский

Citations

129
More than Just a Monolayer: the Multifaceted Role of Endothelial Cells in the Pathophysiology of Atherosclerosis DOI Creative Commons
Marion Mußbacher, Klaudia Schossleitner, Julia B. Kral‐Pointner

et al.

Current Atherosclerosis Reports, Journal Year: 2022, Volume and Issue: 24(6), P. 483 - 492

Published: April 11, 2022

Abstract Purpose of the Review In this review, we summarize current insights into versatile roles endothelial cells in atherogenesis. Recent Findings The vascular endothelium represents first barrier that prevents entry lipoproteins and leukocytes vessel wall, thereby controlling two key events pathogenesis atherosclerosis. Disturbance homeostasis increases permeability, inflammation, cellular trans-differentiation, which not only promotes build-up atherosclerotic plaques but is also involved life-threatening thromboembolic complications such as plaque rupture erosion. focus on recent findings lipoprotein transport, transitions, function. Summary By using cutting-edge technologies single-cell sequencing, epigenetics, cell fate mapping, novel regulatory mechanisms phenotypes have been discovered, challenged established concepts activation, led to a different view disease.

Language: Английский

Citations

51
Mechanisms and clinical implications of endothelium-dependent vasomotor dysfunction in coronary microvasculature DOI
Sharif A. Sabe, Jun Feng, Frank W. Sellke

et al.

AJP Heart and Circulatory Physiology, Journal Year: 2022, Volume and Issue: 322(5), P. H819 - H841

Published: March 25, 2022

Coronary microvascular disease (CMD), which affects the arterioles and capillary endothelium that regulate myocardial perfusion, is an increasingly recognized source of morbidity mortality, particularly in setting metabolic syndrome. The coronary plays a pivotal role maintaining homeostasis, though factors such as diabetes, hypertension, hyperlipidemia, obesity can contribute to endothelial injury consequently arteriolar vasomotor dysfunction. These disturbances microvasculature clinically manifest diminished flow reserve, known independent risk factor for cardiac death, even absence macrovascular atherosclerotic disease. Therefore, growing body literature has examined molecular mechanisms by occurs at level consequences on responses. This review will begin with overview normal physiology, modalities measuring function, clinical implications CMD. introductory topics be followed discussion recent advances understanding inflammation, oxidative stress, insulin resistance, shear cell senescence, tissue ischemia dysregulate homeostasis function.

Language: Английский

Citations

40
The protective roles of citrus flavonoids, naringenin, and naringin on endothelial cell dysfunction in diseases DOI Creative Commons
Joy A. Adetunji, Kehinde D. Fasae, Ayobami Awe

et al.

Heliyon, Journal Year: 2023, Volume and Issue: 9(6), P. e17166 - e17166

Published: June 1, 2023

The endothelial cells (ECs) make up the inner lining of blood vessels, acting as a barrier separating and tissues in several organs. ECs maintain endothelium integrity by controlling constriction relaxation vasculature, fluidity, adhesion, migration. These actions are efficiently coordinated via an intricate signaling network connecting receptors, wide range cellular macromolecules. naturally quiescent i.e.; they not stimulated do proliferate. Upon infection or disease, become activated, this alteration is pivotal pathogenesis spectrum human neurological, cardiovascular, diabetic, cancerous, viral diseases. Considering central position that play disease pathogenesis, therapeutic options have been targeted at improving integrity, assembly, functioning, health. dietary intake flavonoids present citrus fruits has associated with reduced risk dysfunction. Naringenin (NGN) Naringin (NAR), major grapefruit, tomatoes, oranges possess anti-inflammatory, antioxidant properties, cell survival potentials, which improve health vascular endothelium. In review, we provide comprehensive summary advances understanding mechanisms through NGN NAR modulate biomarkers dysfunction protect against unresolved inflammation, oxidative stress, atherosclerosis, angiogenesis. We also perspectives suggest further studies will help assess efficacy therapeutics

Language: Английский

Citations

27
Oxidative Stress and MicroRNAs in Endothelial Cells under Metabolic Disorders DOI Creative Commons
Morgan Minjares,

Wendy Wu,

Jie‐Mei Wang

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(9), P. 1341 - 1341

Published: May 8, 2023

Reactive oxygen species (ROS) are radical intermediates that serve as important second messengers in signal transduction. However, when the accumulation of these molecules exceeds buffering capacity antioxidant enzymes, oxidative stress and endothelial cell (EC) dysfunction occur. EC shifts vascular system into a pro-coagulative, proinflammatory state, thereby increasing risk developing cardiovascular (CV) diseases metabolic disorders. Studies have turned to investigation microRNA treatment for CV factors, post-transcription regulators known co-regulate ROS. In this review, we will discuss ROS pathways generation, normal physiology ROS-induced dysfunction, current knowledge common disorders their connection stress. Therapeutic strategies based on microRNAs response microRNA’s regulatory roles controlling also be explored. It is gain an in-depth comprehension mechanisms generating how manipulating enzymatic byproducts can protect function from prevent development

Language: Английский

Citations

24
SIRT1 Regulation in Ageing and Obesity DOI Creative Commons

Patricia S. Pardo,

Aladin M. Boriek

Mechanisms of Ageing and Development, Journal Year: 2020, Volume and Issue: 188, P. 111249 - 111249

Published: April 19, 2020

Language: Английский

Citations

67
Anthocyanins attenuate endothelial dysfunction through regulation of uncoupling of nitric oxide synthase in aged rats DOI Creative Commons

Geum‐Hwa Lee,

The‐Hiep Hoang, Eun‐Soo Jung

et al.

Aging Cell, Journal Year: 2020, Volume and Issue: 19(12)

Published: Dec. 1, 2020

Endothelial dysfunction is one of the main age-related arterial phenotypes responsible for cardiovascular disease (CVD) in older adults. This endothelial results from decreased bioavailability nitric oxide (NO) arising downstream oxidative stress. In this study, we investigated protective effect anthocyanins and underlying mechanism rat thoracic aorta human vascular cells aging models. vitro, cyanidin-3-rutinoside (C-3-R) cyanidin-3-glucoside (C-3-G) inhibited d-galactose (d-gal)-induced senescence cells, as indicated by reduced senescence-associated-β-galactosidase activity, p21, p16INK4a . Anthocyanins blocked d-gal-induced reactive oxygen species (ROS) formation NADPH oxidase activity. reversed d-gal-mediated inhibition synthase (eNOS) serine phosphorylation SIRT1 expression, recovering NO level cells. Also, SIRT1-mediated eNOS deacetylation was shown to be involved anthocyanin-enhanced vivo, anthocyanin-rich mulberry extract administered rats 8 weeks. alleviated stress rats. Consistently, also raised serum levels, increased eNOS, nitrotyrosine aortas. The acetylation higher group restored treatment. Similarly, associated with plus group. These findings indicate that protect against through enhanced regulating ROS reducing uncoupling.

Language: Английский

Citations

67