Endothelial senescence and microRNA

2012 ◽  
Vol 3 (3) ◽  
pp. 213-223 ◽  
Author(s):  
Munekazu Yamakuchi
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Cellular Senescence ◽  
Vascular Diseases ◽  
Cell Senescence ◽  
Factors Affecting ◽  
New Treatments

AbstractCellular senescence occurs when cells lose the ability to divide and proliferate. Endothelial cell senescence is associated with vascular diseases, such as atherosclerosis. In this review, I discuss the factors affecting endothelial cell senescence. Then I describe the role of microRNAs (miRNAs) in endothelial cell senescence. Understanding miRNA pathways in endothelial senescence may lead to new treatments for endothelial dysfunction and atherosclerosis.

O42. l-Arginine accelerates endothelial cell senescence. Role of arginine transporters and arginase

Nitric Oxide ◽  
2008 ◽  
Vol 19 ◽  
pp. 29
Author(s):  
Eva D.M. Flick ◽  
Fortunato Scalera ◽  
Ellen I. Closs ◽  
Jean-Paul Boissel ◽  
Jens Martens-Lobenhoffer ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Senescence

THE ROLE OF INFLAMMATION AND ENDOTHELIAL CELL ACTIVATION IN HYPERTENSIVE CHILDREN WITH ENDOTHELIAL DYSFUNCTION

2011 ◽  
Vol 29 ◽  
pp. e337
Author(s):  
M. Andor ◽  
O. Margineanu ◽  
M. Tomescu ◽  
D. Lighezan ◽  
R. Christodorescu ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Cell Activation ◽  
Endothelial Cell Activation

scholarly journals 197 ENDOTHELIAL CELL SENESCENCE: THE ROLE OF SIRT6

Heart ◽  
2013 ◽  
Vol 99 (suppl 2) ◽  
pp. A109.2-A110 ◽  
Author(s):  
J Erusalimsky ◽  
A Uryga
Keyword(s):  
Endothelial Cell ◽  
Cell Senescence

Novel role of PKR in palmitate-induced Sirt1 inactivation and endothelial cell senescence

2018 ◽  
Vol 315 (3) ◽  
pp. H571-H580 ◽  
Author(s):  
Yapei Li ◽  
Zhouyangfan Peng ◽  
Chunle Wang ◽  
Le Li ◽  
Yiping Leng ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cardiovascular Diseases ◽  
Protein Kinase ◽  
Umbilical Vein ◽  
Cell Senescence ◽  
Sirtuin 1 ◽  
Dependent Protein Kinase ◽  
Human Umbilical Vein ◽  
Dependent Protein

Endothelial cell senescence is regarded as a vital characteristic of cardiovascular diseases. Elevated palmitate (PA) is an independent risk factor of cardiovascular diseases, but its role in endothelial cell senescence is currently unknown. During the course of studying the prosenescent role of PA, we discovered a key role of dsRNA-dependent protein kinase [protein kinase R (PKR)] in endothelial senescence. Exposure of human umbilical vein endothelial cells (HUVECs) to PA-induced cell senescence is characterized by increased levels of senescence-associated β-galactose glucosidase activity, excessive production of reactive oxygen species production, impaired cellular proliferation, and G1 phase arrest. This phenomenon is associated with an increase of PKR autophosphorylation and decreased activity of sirtuin 1 (Sirt1), a pivotal antisenescent factor. PKR inactivation by PKR siRNA or its phosphorylation inhibitor 2-aminopurine significantly attenuated PA-induced HUVEC senescence by reversing Sirt1 activity and its downstream signaling. Moreover, to study the regulatory mechanism between PKR and Sirt1, we found that PKR promotes JNK activation to inhibit Sirt1 activity and that this effect could be reversed by the JNK inhibitor SP600125. These findings provide evidence that PKR mediates PA-induced HUVEC senescence by inhibiting Sirt1 signaling. Our study provides novel insights into the actions and mechanisms of PKR in endothelial senescence. NEW & NOTEWORTHY This study first provides a novel observation that dsRNA-dependent protein kinase (PKR) mediates palmitate-induced sirtuin 1 inactivation and subsequent human umbilical vein endothelial cell senescence. Most importantly, these new findings will provide a potential therapeutic strategy to improve free fatty acid-induced endothelial senescence by targeting PKR in cardiovascular diseases.

scholarly journals Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function

2017 ◽  
Vol 313 (5) ◽  
pp. H890-H895 ◽  
Author(s):  
Matthew J. Rossman ◽  
Rachelle E. Kaplon ◽  
Sierra D. Hill ◽  
Molly N. McNamara ◽  
Jessica R. Santos-Parker ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Cell Senescence ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Vascular Endothelial Function ◽  
Healthy Humans ◽  
Age Related ◽  
Habitual Exercise

Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction. Protein expression (quantitative immunofluorescence) of p53, a transcription factor related to increased cellular senescence, and the cyclin-dependent kinase inhibitors p21 and p16 were 116%, 119%, and 128% greater (all P < 0.05), respectively, in ECs obtained from antecubital veins of older sedentary (60 ± 1 yr, n = 12) versus young sedentary (22 ± 1 yr, n = 9) adults. These age-related differences were not present (all P > 0.05) in venous ECs from older exercising adults (57 ± 1 yr, n = 13). Furthermore, venous EC protein levels of p53 ( r = −0.49, P = 0.003), p21 ( r = −0.38, P = 0.03), and p16 ( r = −0.58, P = 0.002) were inversely associated with vascular endothelial function (brachial artery flow-mediated dilation). Similarly, protein expression of p53 and p21 was 26% and 23% higher (both P < 0.05), respectively, in ECs sampled from brachial arteries of healthy older sedentary (63 ± 1 yr, n = 18) versus young sedentary (25 ± 1 yr, n = 9) adults; age-related changes in arterial EC p53 and p21 expression were not observed ( P > 0.05) in older habitually exercising adults (59 ± 1 yr, n = 14). These data indicate that EC senescence is associated with sedentary aging and is linked to endothelial dysfunction. Moreover, these data suggest that prevention of EC senescence may be one mechanism by which aerobic exercise protects against endothelial dysfunction with age. NEW & NOTEWORTHY Our study provides novel evidence in humans of increased endothelial cell senescence with sedentary aging, which is associated with impaired vascular endothelial function. Furthermore, our data suggest an absence of age-related increases in endothelial cell senescence in older exercising adults, which is linked with preserved vascular endothelial function. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/aging-exercise-and-endothelial-cell-senescence/ .

Anthracycline-Induced Cardiotoxicity: The Role of Endothelial Dysfunction

Cardiology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Elena V. Grakova ◽  
Sergey N. Shilov ◽  
Kristina V. Kopeva ◽  
Ekaterina N. Berezikova ◽  
Anna A. Popova ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Genetic Factors ◽  
Vascular Toxicity ◽  
Endothelin 1 ◽  
Endothelial Cell Death ◽  
Endothelial Nitric Oxide ◽  
Genetic Susceptibility Factor

Cardiovascular disease remains the leading cause of mortality accounting up to 40% of all deaths, but, currently, cancer is prominent cause of death globally. Anthracyclines are the cornerstone of chemotherapy in women with breast cancer. However, its clinical use is limited by their cardiotoxic effects that can trigger heart failure development. Vascular toxicity of chemotherapy may be linked with endothelial dysfunction because anthracycline damage of endothelial cells can lead to the development and progression of cardiomyopathy by decreasing the release and activity of endothelial factors and, ultimately, endothelial cell death. These processes suppress anti-inflammatory and vascular reparative functions and initiate the development of future cardiovascular events. Recent studies have shown that chemotherapy may induce toxicity in the vascular endothelium and is accompanied by systemic endothelial dysfunction in patients with diagnosed cardiovascular diseases. Because the initial endothelial cell insult is likely asymptomatic, there is often a long delay between the termination of doxorubicin therapy and the onset of vascular disorders. In this case, genetic susceptibility factor will help to identify susceptible patients in the future. The objectives of this study were to evaluate prognostic role of molecular (endothelin-1) and genetic factors (gene polymorphisms of endothelial nitric oxide (NO) synthase (NOS3, rs1799983), endothelin-1 receptor type A (EDNRA, C+70G, rs5335) and NADPH oxidase (C242T, rs4673) in development of endothelial dysfunction and anthracycline-induced cardiotoxicity in women without cardiovascular diseases.

Abstract 51: Effects of Human Immunodeficiency Virus-1 gp120 Viral Proteins on Endothelial Senescence and microRNA Expression

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Jamie Hijmans ◽  
Kelly Stockelman ◽  
Whitney Reiakvam ◽  
Ma’ayan Levy ◽  
Lillian Bruster ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Endothelial Cell ◽  
Cellular Senescence ◽  
Viral Protein ◽  
Disease Risk ◽  
Cell Damage ◽  
Cell Senescence ◽  
Cellular Expression ◽  
Immunodeficiency Virus ◽  
Hiv 1

Human immunodeficiency virus (HIV)-1 is associated with profound endothelial cell damage and dysfunction. HIV-1 envelope glycoprotein 120 (gp120) is a toxic viral protein released from infected cells and promotes endothelial cell dysfunction. Endothelial cell senescence is a key factor underlying endothelial dysfunction and, in turn, vascular disease risk. It is now clear that microRNAs (miRs) play a pivotal role in regulating cellular senescence. The aim of this study was to determine whether gp120 induces endothelial cell senescence; and if so, whether the cellular expression of senescence-related miRs (mir-34a, -146a and -217) are adversely affected by gp120. Cultured HAECs (3 rd passage) were plated at a density of 5.0x10 5 cells/condition. Cells were treated with media alone or media containing gp120: either lav gp120 (X4; 100ng/mL) or Bal gp120 (R5; 100ng/mL) for 24 h. Thereafter, cells were stained for senescence-associated β-galactosidase (β-gal) for 14 h. Cells from 5-7 random microscope fields were counted and (%) senescence was calculated as the ratio of β-gal positive cells to total cells. To determine miR expression, RNA was extracted from 1.0x10 5 cells and was quantified using RT-PCR. Cellular expression was normalized to RNU6 and calculated as fold change in ΔΔCt from control (N=4, experimental units). Both X4 (32.0±0.7% vs 18.3±1.7%) and R5 (30.2±3.8% vs 18.3±1.7%) significantly increased cellular senescence vs control. Moreover, the magnitude of increase (~65%) in senescent cells was similar between the glycoproteins. Cellular expression of pro-senescence miR-34a (1.60±0.04 fold) was increased (~60%; P<0.05) in response to X4 treatment compared with control. However, expression of miR-146a (1.34±0.36 fold) and miR-217 (1.38±0.36 fold) was not significantly affected by X4. In response to R5, cellular expression of miR-34a (1.23±0.07 fold) was significantly increased (~23%) and miR-146a (1.23±0.07 fold) was significantly decreased (~80%); miR-217 was not influenced by R5 (1.05±0.13 fold). These data indicate that HIV-1 viral protein gp120 induces endothelial cell senescence and adversely affects cellular expression of senescence-associated miRs. miR dysregulation may underlie the pro-senescent effects of gp120.

scholarly journals Cellular senescence is a promising target for chronic wounds: a comprehensive review

2020 ◽  
Vol 8 ◽  
Author(s):  
Ziwen Wang ◽  
Chunmeng Shi
Keyword(s):  
Cellular Senescence ◽  
Therapeutic Strategy ◽  
Chronic Wounds ◽  
Pathological Process ◽  
Cell Senescence ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Promising Target ◽  
Radiation Ulcers ◽  
New Treatments

Abstract Chronic wounds include, but are not limited to, radiation ulcers, pressure ulcers, vascular ulcers and diabetic foot ulcers. These chronic wounds can persist for years without healing and severe ulcers may lead to amputation. Unfortunately, the underlying pathologies of refractory chronic wounds are not fully characterized, and new treatments are urgently needed. Recently, increasing evidence has indicated that cell senescence plays an important role in the development of chronic wounds, and preventing cell senescence or removing senescent cells holds promise as a new therapeutic strategy. In this review, we aim to probe these latest findings to promote the understanding of cellular senescence in the pathological process and potential management of chronic wounds.

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