scholarly journals Atherogenic Factors and Their Epigenetic Relationships

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Ana Z. Fernandez ◽  
Andrew L. Siebel ◽  
Assam El-Osta
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Dna Methylation ◽  
Smooth Muscle ◽  
Immune Cells ◽  
Human Disease ◽  
Physiology And Biochemistry ◽  
Histone Modifying Enzymes ◽  
Atherosclerotic Process

Hypercholesterolemia, homocysteine, oxidative stress, and hyperglycemia have been recognized as the major risk factors for atherogenesis. Their impact on the physiology and biochemistry of vascular cells has been widely demonstrated for the last century. However, the recent discovery of the role of epigenetics in human disease has opened up a new field in the study of atherogenic factors. Thus, epigenetic tags in endothelial, smooth muscle, and immune cells seem to be differentially affected by similar atherogenic stimuli. This paper summarizes some recent works on expression of histone-modifying enzymes and DNA methylation directly linked to the presence of risk factors that could lead to the development or prevention of the atherosclerotic process.

An AraC/XylS Family Transcriptional Regulator Modulates the Oxidative Stress Response of Francisella tularensis

2021 ◽  
Author(s):  
Dina Marghani ◽  
Zhuo Ma ◽  
Anthony J. Centone ◽  
Weihua Huang ◽  
Meenakshi Malik ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Francisella Tularensis ◽  
Human Disease ◽  
Transcriptional Regulator ◽  
Intracellular Survival ◽  
Gram Negative ◽  
Expression Of Genes ◽  
Transcription Regulators

Francisella tularensis is a Gram-negative bacterium that causes a fatal human disease known as tularemia. The Centers for Disease Control have classified F. tularensis as Category A Tier-1 Select Agent. The virulence mechanisms of Francisella are not entirely understood. Francisella possesses very few transcription regulators, and most of these regulate the expression of genes involved in intracellular survival and virulence. The F. tularensis genome sequence analysis reveals an AraC ( FTL_ 0689) transcriptional regulator homologous to the AraC/XylS family of transcriptional regulators. In Gram-negative bacteria, AraC activates genes required for L-arabinose utilization and catabolism. The role of the FTL_ 0689 regulator in F. tularensis is not known. In this study, we characterized the role of FTL_ 0689 in gene regulation of F. tularensis and investigated its contribution to intracellular survival and virulence. The results demonstrate that FTL_0689 in Francisella is not required for L-arabinose utilization. Instead, FTL_ 0689 specifically regulates the expression of the oxidative and global stress response, virulence, metabolism, and other key pathways genes required by Francisella when exposed to oxidative stress. The FTL_0689 mutant is attenuated for intramacrophage growth and virulence in mice. Based on the deletion mutant phenotype, FTL_0689 was termed osrR ( o xidative s tress r esponse r egulator). Altogether, this study elucidates the role of the osrR transcriptional regulator in tularemia pathogenesis. IMPORTANCE: The virulence mechanisms of category A select agent Francisella tularensis , the causative agent of a fatal human disease known as tularemia, remain largely undefined. The present study investigated the role of a transcriptional regulator and its overall contribution to the oxidative stress resistance of F. tularensis . The results provide an insight into a novel gene regulatory mechanism, especially when Francisella is exposed to oxidative stress conditions. Understanding such Francisella - specific regulatory mechanisms will identify potential targets for developing effective therapies and vaccines to prevent tularemia.

scholarly journals Predictive Role of F2-Isoprostanes as Biomarkers for Brain Damage after Neonatal Surgery

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
L. J. Stolwijk ◽  
P. M. A. Lemmers ◽  
M. Y. A. van Herwaarden ◽  
D. C. van der Zee ◽  
F. van Bel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Brain Injury ◽  
Multivariable Analysis ◽  
Major Surgery ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
Significant Difference ◽  
Predictive Role

Objective. Neonates have a high risk of oxidative stress during anesthetic procedures. The predictive role of oxidative stress biomarkers on the occurrence of brain injury in the perioperative period has not been reported before. Methods. A prospective cohort study of patients requiring major surgery in the neonatal period was conducted. Biomarker levels of nonprotein-bound iron (NPBI) in plasma and F2-isoprostane in plasma and urine before and after surgical intervention were determined. Brain injury was assessed using postoperative MRI. Results. In total, 61 neonates were included, median gestational age at 39 weeks (range 31–42) and weight at 3000 grams (1400–4400). Mild to moderate brain lesions were found in 66%. Logistic regression analysis showed a significant difference between plasma NPBI in patients with nonparenchymal injury versus no brain injury: 1.34 umol/L was identified as correlation threshold for nonparenchymal injury (sensitivity 67%, specificity 91%). In the multivariable analysis, correcting for GA, no other significant relation was found with the oxidative stress biomarkers and risk factors. Conclusion. Oxidative stress seems to occur during anaesthesia in this cohort of neonates. Plasma nonprotein-bound iron showed to be associated with nonparenchymal injury after surgery, with values of 1.34 umol/L or higher. Risk factors should be elucidated in a more homogeneous patient group.

The pro-oxidant role of methylglyoxal in mesenteric artery smooth muscle cells

2005 ◽  
Vol 83 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Lingyun Wu
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mesenteric Artery ◽  
Advanced Glycation Endproducts ◽  
Muscle Cells ◽  
Heme Oxygenase 1 ◽  
Rat Mesenteric Artery ◽  
Cultured Smooth Muscle Cells

Methylglyoxal (MG), a highly reactive metabolite of glucose, causes non-enzymatic glycation of proteins to form irreversible advanced glycation endproducts (AGEs). The present study investigated whether methylglyoxal induced oxidative stress and activated nuclear factor kappa B (NF-κB) in freshly isolated and cultured smooth muscle cells (SMCs) from rat mesenteric artery. The treatment of cells with MG (50 or 100 µmol/L) induced a significant increase in AGE formation and oxidation of DCF. MG-enhanced generation of AGEs and the oxidation of DCF was markedly inhibited by antioxidant n-acetylcysteine (NAC, 600 µmol/L). MG at a concentration of 100 µmol/L increased the heme-oxygenase-1 expression in these cells. Moreover, MG activated NF-κB p65, indicated by an increased im muno cytochemistry stain for NF-κB p65 located in the nucleus after the treatment of mesenteric artery SMCs with MG. MG-induced activation of NF-κB p65 was inhibited by NAC. In summary, MG significantly increases oxidative stress and activates NF-κB p65 in mesenteric artery SMCs. The pro-oxidant role of methylglyoxal may contribute to various pathological changes of SMCs from resistance arteries.Key words: methylglyoxal, oxidative stress, NF-κB p65, vascular smooth muscle cells, mesenteric artery.

Role of oxidative stress in angiotensin II-induced enhanced expression of Giα proteins and adenylyl cyclase signaling in A10 vascular smooth muscle cells

2007 ◽  
Vol 292 (4) ◽  
pp. H1922-H1930 ◽  
Author(s):  
Yuan Li ◽  
Georgios Lappas ◽  
Madhu B. Anand-Srivastava
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Adenylyl Cyclase ◽  
Vascular Smooth Muscle Cells ◽  
Ang Ii ◽  
Enhanced Expression

We have previously reported that angiotensin II (ANG II) treatment of A10 vascular smooth muscle cells (VSMCs) increased inhibitory G proteins (Gi protein) expression and associated adenylyl cyclase signaling which was attributed to the enhanced MAP kinase activity. Since ANG II has been shown to increase oxidative stress, we investigated the role of oxidative stress in ANG II-induced enhanced expression of Giα proteins and examined the effects of antioxidants on ANG II-induced enhanced expression of Giα proteins and associated adenylyl cyclase signaling in A10 VSMCs. ANG II treatment of A10 VSMCs enhanced the production of O2− and the expression of Nox4 and P47phox, different subunits of NADPH oxidase, which were attenuated toward control levels by diphenyleneiodonium (DPI). In addition, ANG II augmented the expression of Giα-2 and Giα-3 proteins in a concentration- and time-dependent manner; the maximal increase in the expression of Giα was observed at 1 to 2 h and at 0.1–1.0 μM. The enhanced expression of Giα-2 and Giα-3 proteins was restored to control levels by antioxidants such as N-acetyl-l-cysteine, α-tocopherol, DPI, and apocynin. In addition, ANG II also enhanced the ERK1/2 phosphorylation that was restored to control levels by DPI. Furthermore, the inhibition of forskolin-stimulated adenylyl cyclase activity by low concentrations of 5′- O-(3-triotriphosphate) (receptor-independent Gi functions) and ANG II-, des(Glu18,Ser19,Glu20,Leu21,Gly22)atrial natriuretic peptide4-23-NH2 (natriuretic peptide receptor-C agonist), and oxotremorine-mediated inhibitions of adenylyl cyclase (receptor-dependent functions) that were augmented in ANG II-treated VSMCs was also restored to control levels by antioxidant treatments. In addition, Gsα-mediated diminished stimulation of adenylyl cyclase by stimulatory hormones in ANG II-treated cells was also restored to control levels by DPI. These results suggest that ANG II-induced enhanced levels of Giα proteins and associated functions in VSMCs may be attributed to the ANG II-induced enhanced oxidative stress, which exerts its effects through mitogen-activated protein kinase signaling pathway.

scholarly journals The prevalence of risk factors of cardiovascular diseases in persons with arterial hypertension exposed to occupational stress

2017 ◽  
Vol 95 (6) ◽  
pp. 535-544
Author(s):  
A. I. Telegina ◽  
R. A. Liferov ◽  
A. Ya. Fisun ◽  
R. G. Makiev ◽  
V. V. Gornov ◽  
...  
Keyword(s):  
Risk Factors ◽  
Occupational Stress ◽  
Emotional Stress ◽  
Cardiovascular Complications ◽  
Leading Role ◽  
High Prevalence ◽  
Atherosclerotic Process ◽  
High Level

Based on the literature data and the results of their own research, the authors emphasize the importance of studying adverse effects of high emotional load during stress-induced hypertension and draw attention to the high prevalence of modifiable risk factors of cardiovascular disease among servicemen exposed to occupational stress. It has been shown that lifestyle of hypertensive subjects under heavy stress is characterized by irrational changes in eating behavior, high prevalence of smoking, increased alcohol consumption, and low physical activity. The leading role of long-term emotional stress was demonstrated as an independent risk factor of hypertension in servicemen exposed to long-term occupational psycho-emotional stress. Analysis of the intima-media complex thickness in brachiocephalic arteries, depending on the level of psychosocial stress demonstrated that the group of the examined servicemen with hypertension showed changes that might be due to the development of atherosclerotic process, the response to increased flow, and arterial wall tension at a high level of stress. These changes are unidirectional regardless of the duration of hypertension history. Results of evaluation of the overall risk of developing cardiovascular complications based on the SCORE scale in the servicemen with established and newly diagnosed hypertension under heavy stress suggest its enhancement in the next 10 years which makes necessary implementation of a system of measures for preventing and correcting pathological conditions caused by stressful loads. Stratification of risk factors is essential for early diagnosis of hypertension and the choice of adequate therapy in subjects undergoing high psycho-emotional stress.

scholarly journals Different DNA methylome, transcriptome and histological features in uterine fibroids with and without MED12 mutations

2021 ◽  
Author(s):  
Ryo Maekawa ◽  
Shun Sato ◽  
Tetsuro Tamehisa ◽  
Takahiro Sakai ◽  
Takuya Kajimura ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Blood Vessels ◽  
Uterine Fibroids ◽  
Muscle Cells ◽  
Histological Features ◽  
Dna Methylome

Abstract Background: Somatic mutations in Mediator complex subunit 12 (MED12m) have been reported as a biomarker of uterine fibroids (UFs). However, the role of MED12m is still unclear in the pathogenesis of UFs. Therefore, we investigated the differences in DNA methylome, transcriptome, and histological features between MED12m-positive and -negative UFs. Methods: DNA methylomes and transcriptomes were obtained from MED12m-positive and -negative UFs and myometrium, and hierarchically clustered. Differentially expressed genes in comparison with the myometrium and co-expressed genes detected by weighted gene co-expression network analysis were subjected to gene ontology enrichment analyses. The amounts of collagen fibers and the number of blood vessels and smooth muscle cells were histologically evaluated. Results: Hierarchical clustering based on DNA methylation clearly separated the myometrium, MED12m-positive, and MED12m-negative UFs. MED12m-positive UFs had the increased activities of extracellular matrix formation, whereas MED12m-negative UFs had the increased angiogenic activities and smooth muscle cell proliferation. Conclusion: The MED12m-positive and -negative UFs had different DNA methylation, gene expression, and histological features. The MED12m-positive UFs form the tumor with a rich extracellular matrix and poor blood vessels and smooth muscle cells compared to the MED12m-negative UFs, suggesting MED12 mutations affect the tissue composition of UFs.

Pesticides-induced cardiovascular dysfunctions: Prevalence and associated mechanisms

2021 ◽  
Vol 17 ◽  
Author(s):  
Joseph A. Adeyemi ◽  
Victor O. Ukwenya ◽  
Olatunbosun K. Arowolo ◽  
Christian C. Olise
Keyword(s):  
Public Health ◽  
Oxidative Stress ◽  
Risk Factors ◽  
Cardiovascular Diseases ◽  
Chronic Exposure ◽  
Human Exposure ◽  
Laboratory Data ◽  
Oxygen Species ◽  
Pathological Conditions

: Increased applications of pesticides mainly in agriculture and public health has resulted in increased chances of human exposure to pesticides. Chronic exposure to pesticides has been implicated in several human diseases including cardiovascular diseases. Cardiovascular diseases are broadly used for various heart pathological conditions including defect blood vessels, and they include myocardial infarction, atherosclerosis, stroke, cardiomyopathy, coronary heart disease etc. In this review, the association between human exposure to pesticides and development of cardiovascular diseases was discussed using epidemiological and laboratory data. The toxicokinetics of pesticides in humans was reviewed, as well as the risk factors for cardiovascular diseases. The important role of oxidative stress, and principally the induction of reactive oxygen species as the signaling molecules for various signaling pathways involved in pesticidesinduced cardiovascular disease was discussed.

scholarly journals Bladder function in mice with inducible smooth muscle-specific deletion of the manganese superoxide dismutase gene

2015 ◽  
Vol 309 (3) ◽  
pp. C169-C178 ◽  
Author(s):  
Guiming Liu ◽  
Rania A. Elrashidy ◽  
Nan Xiao ◽  
Michael Kavran ◽  
Yexiang Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Smooth Muscle ◽  
Manganese Superoxide Dismutase ◽  
Bladder Function ◽  
Antioxidant Systems ◽  
Wild Type ◽  
Manganese Superoxide ◽  
Specific Deletion

Manganese superoxide dismutase (MnSOD) is considered a critical component of the antioxidant systems that protect against oxidative damage. We are interested in the role of oxidative stress in bladder detrusor smooth muscle (SM) in different disease states. In this study, we generated an inducible, SM-specific Sod2−/− mouse model to investigate the effects of MnSOD depletion on the function of the bladder. We crossbred floxed Sod2 ( Sod2lox/lox) mice with mice containing heterozygous knock-in of a gene encoding a tamoxifen-activated Cre recombinase in the SM22α promoter locus [SM-CreERT2(ki)Cre/+]. We obtained Sod2lox/lox,SM-CreERT2(ki)Cre/+ mice and injected 8-wk-old males with 4-hydroxytamoxifen to induce Cre-mediated excision of the floxed Sod2 allele. Twelve weeks later, SM-specific deletion of Sod2 and depletion of MnSOD were confirmed by polymerase chain reaction, immunoblotting, and immunohistochemistry. SM-specific Sod2−/− mice exhibited normal growth with no gross abnormalities. A significant increase in nitrotyrosine concentration was found in bladder SM tissue of SM-specific Sod2−/− mice compared with both wild-type mice and Sod2+/+, SM-CreERT2(ki)Cre/+ mice treated with 4-hydroxytamoxifen. Assessment of 24-h micturition in SM-specific Sod2−/− mice revealed significantly higher voiding frequency compared with both wild-type and SM-specific Cre controls. Conscious cystometry revealed significantly shorter intercontraction intervals and lower functional bladder capacity in SM-specific Sod2−/− mice compared with wild-type mice. This novel model can be used for exploring the mechanistic role of oxidative stress in organs rich in SM in different pathological conditions.

Sign in / Sign up

Export Citation Format

Share Document