scholarly journals Transcriptomic Bioinformatic Analyses of Atria Uncover Involvement of Pathways Related to Strain and Post-translational Modification of Collagen in Increased Atrial Fibrillation Vulnerability in Intensely Exercised Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Yena Oh ◽  
Sibao Yang ◽  
Xueyan Liu ◽  
Sayantan Jana ◽  
Farzad Izaddoustdar ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cardiovascular Health ◽  
Venous Pressure ◽  
Post Translational Modification ◽  
Time Points ◽  
Ventricular Structure ◽  
And Function ◽  
Collagen Genes ◽  
Necrosis Factor

Atrial Fibrillation (AF) is the most common supraventricular tachyarrhythmia that is typically associated with cardiovascular disease (CVD) and poor cardiovascular health. Paradoxically, endurance athletes are also at risk for AF. While it is well-established that persistent AF is associated with atrial fibrosis, hypertrophy and inflammation, intensely exercised mice showed similar adverse atrial changes and increased AF vulnerability, which required tumor necrosis factor (TNF) signaling, even though ventricular structure and function improved. To identify some of the molecular factors underlying the chamber-specific and TNF-dependent atrial changes induced by exercise, we performed transcriptome analyses of hearts from wild-type and TNF-knockout mice following exercise for 2 days, 2 or 6 weeks of exercise. Consistent with the central role of atrial stretch arising from elevated venous pressure in AF promotion, all 3 time points were associated with differential regulation of genes in atria linked to mechanosensing (focal adhesion kinase, integrins and cell-cell communications), extracellular matrix (ECM) and TNF pathways, with TNF appearing to play a permissive, rather than causal, role in gene changes. Importantly, mechanosensing/ECM genes were only enriched, along with tubulin- and hypertrophy-related genes after 2 days of exercise while being downregulated at 2 and 6 weeks, suggesting that early reactive strain-dependent remodeling with exercise yields to compensatory adjustments. Moreover, at the later time points, there was also downregulation of both collagen genes and genes involved in collagen turnover, a pattern mirroring aging-related fibrosis. By comparison, twofold fewer genes were differentially regulated in ventricles vs. atria, independently of TNF. Our findings reveal that exercise promotes TNF-dependent atrial transcriptome remodeling of ECM/mechanosensing pathways, consistent with increased preload and atrial stretch seen with exercise. We propose that similar preload-dependent mechanisms are responsible for atrial changes and AF in both CVD patients and athletes.

Abstract MP03: Plasma Sphingolipids and Risks of Heart Failure and Atrial Fibrillation in Older Adults: The Cardiovascular Health Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Rozenn N Lemaitre ◽  
Paul N Jensen ◽  
Barbara McKnight ◽  
Andrew Hoofnagle ◽  
Irena B King ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Fatty Acid ◽  
Lower Risk ◽  
Cardiovascular Health ◽  
Biological Activities ◽  
Experimental Studies ◽  
Health Study ◽  
Cardiovascular Health Study

Introduction: Ceramides and sphingomyelins (sphingolipids) are circulating lipids involved in multiple physiological pathways relevant to heart failure (HF) and atrial fibrillation (AF), including apoptosis, oxidative stress, and inflammation. Experimental studies suggest that sphingolipids with different saturated fatty acids exhibit different biological activities, but their relationships with HF and AF are unknown. Hypothesis: Higher levels of plasma ceramide and sphingomyelin that contain the fatty acid 16:0 are associated with higher risks of HF and AF; and higher levels of ceramides and sphingomyelins that contain the fatty acid 20:0, 22:0 or 24:0 are associated with lower risks. Methods: We measured sphingolipids in the Cardiovascular Health Study (CHS) in plasma samples from 1994-95 (N=4026) or from 1992-93 (N=586). We assessed the separate associations of the levels of 8 sphingolipids with risks of incident HF and incident AF using Cox regression. A p-value threshold of 0.006 was used to account for multiple testing. Results: Among 4,612 participants, 1179 incident HF and 1198 incident AF occurred during >40,000 person-years of follow-up. In adjusted analyses, higher levels of Cer-16 (ceramide with 16:0) and SM-16 (sphingomyelin with 16:0) were associated with higher risk of incident HF, but not with risk of incident AF (Table). In contrast, higher levels of Cer-20, Cer-22 and Cer-24 were each associated with lower risk of AF, but not with risk of HF. Higher levels of SM-20, SM-22, and SM-24 tended to be associated with lower risks of AF and HF, with only the association of SM-20 with AF significant. Conclusions: Plasma levels of ceramide and sphingomyelin with 16:0 show different associations with HF and AF than species with 20:0, 22:0 or 24:0. Associations of Cer-16 and SM-16 specifically with higher risk of HF may be due to a role of apoptosis in HF. The novel findings that Cer-20, Cer-22, and Cer-24 are associated with lower risk of AF warrant further examination of the role of these sphingolipids in protecting from AF.

scholarly journals The Role of Magnetic Resonance Imaging and Cardiac Computed Tomography in the Assessment of Left Atrial Anatomy, Size, and Function

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Petr Kuchynka ◽  
Jana Podzimkova ◽  
Martin Masek ◽  
Lukas Lambert ◽  
Vladimir Cerny ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Atrial Fibrillation ◽  
Magnetic Resonance ◽  
Left Atrial ◽  
Cardiac Computed Tomography ◽  
Left Atrial Volume ◽  
Detailed Knowledge ◽  
Long Term Outcome ◽  
And Function

In the last decade, there has been increasing evidence that comprehensive evaluation of the left atrium is of utmost importance. Numerous studies have clearly demonstrated the prognostic value of left atrial volume for long-term outcome. Furthermore, advances in catheter ablation procedures used for the treatment of drug-refractory atrial fibrillation require the need for detailed knowledge of left atrial and pulmonary venous morphology as well of atrial wall characteristics. This review article discusses the role of cardiac magnetic resonance and computed tomography in assessment of left atrial size, its normal and abnormal morphology, and function. Special interest is paid to the utility of these rapidly involving noninvasive imaging methods before and after atrial fibrillation ablation.

scholarly journals Autonomous TNF is critical for in vivo monocyte survival in steady state and inflammation

2017 ◽  
Vol 214 (4) ◽  
pp. 905-917 ◽  
Author(s):  
Yochai Wolf ◽  
Anat Shemer ◽  
Michal Polonsky ◽  
Mor Gross ◽  
Alexander Mildner ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mononuclear Phagocytes ◽  
Autoimmune Encephalomyelitis ◽  
Wild Type Counterpart ◽  
And Function ◽  
Necrosis Factor ◽  
Experimental Autoimmune

Monocytes are circulating mononuclear phagocytes, poised to extravasate to sites of inflammation and differentiate into monocyte-derived macrophages and dendritic cells. Tumor necrosis factor (TNF) and its receptors are up-regulated during monopoiesis and expressed by circulating monocytes, as well as effector monocytes infiltrating certain sites of inflammation, such as the spinal cord, during experimental autoimmune encephalomyelitis (EAE). In this study, using competitive in vitro and in vivo assays, we show that monocytes deficient for TNF or TNF receptors are outcompeted by their wild-type counterpart. Moreover, monocyte-autonomous TNF is critical for the function of these cells, as TNF ablation in monocytes/macrophages, but not in microglia, delayed the onset of EAE in challenged animals and was associated with reduced acute spinal cord infiltration of Ly6Chi effector monocytes. Collectively, our data reveal a previously unappreciated critical cell-autonomous role of TNF on monocytes for their survival, maintenance, and function.

scholarly journals The impact of 6 weeks of atrial fibrillation on left atrial and ventricular structure and function

2015 ◽  
Vol 150 (6) ◽  
pp. 1602-1608.e1 ◽  
Author(s):  
Toshinobu Kazui ◽  
Mathew C. Henn ◽  
Yoshiyuki Watanabe ◽  
Sándor J. Kovács ◽  
Christopher P. Lawrance ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Structure And Function ◽  
Ventricular Structure ◽  
And Function ◽  
The Impact

scholarly journals Identification the role of mono-ADP-ribosylation in colorectal cancer by integrated Transcriptome analysis

2021 ◽  
Author(s):  
Shuxian Zhang ◽  
Jiale Duan ◽  
Yanping Yang ◽  
Hanjuan Gong ◽  
Yi Tang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endoplasmic Reticulum ◽  
Alternative Splicing ◽  
Enrichment Analysis ◽  
Drug Candidate ◽  
Post Translational Modification ◽  
Lentiviral Infection ◽  
Whole Transcriptome Sequencing ◽  
And Function

Abstract Purpose Our previous study has clarified the carcinogenic properties of arginine-specific mono-ADP ribosyltransferase 1(ART1), which is considered to be a critical post-translational modification that changes the structure and function of proteins and is widely involved in important processes. This study provides, for the first time, a comprehensive insight of transcriptomic analysis for colorectal cancer cells interfered with ART1 silencing by Illumina RNA-Seq and related verification experiments. Methods Lentiviral infection was used to construct a CT-26 cell line that stably knocks down the ART1 gene, a whole transcriptome sequencing technique was performed to identify differentially expressed genes (DEGs). GO and KEGG classification/enrichment analysis and verification experiments were performed to determine the role of ART1 in the progression of colorectal cancer. Results a total of 5552 DEGs, GO function and KEGG pathway with highest enrichment, forms of SNP and diverse splicing patterns were able to be identified. Importantly, knockdown of ART1 affected the occurrence of the splicing of certain key genes related to tumor cell growth, also down-regulated expression of the key gene PTBP1 for alternative splicing. The overall attenuation of the endoplasmic reticulum unfolded protein response (UPR) signaling pathway caused by ART1 inhibition would unbalance UPR signaling, leading to the occurrence of apoptosis to impede tumorigenesis. Conclusion ART1, which clustered in organelles, may promote the development of colorectal cancer by participating in a variety of new mechanisms including endoplasmic reticulum stress regulation, metabolic process or alternative splicing, which may provide a good clinical drug candidate closer to targeted therapy of CRC.

scholarly journals Plasticizers and Cardiovascular Health: Role of Adipose Tissue Dysfunction

2021 ◽  
Vol 11 ◽  
Author(s):  
Mikyla A. Callaghan ◽  
Samuel Alatorre-Hinojosa ◽  
Liam T. Connors ◽  
Radha D. Singh ◽  
Jennifer A. Thompson
Keyword(s):  
Cardiovascular Disease ◽  
Adipose Tissue ◽  
Adverse Effects ◽  
Cardiovascular Health ◽  
The United States ◽  
Current Evidence ◽  
Endocrine Disrupting ◽  
And Function

Since the 1950s, the production of plastics has increased 200-fold, reaching 360 million tonnes in 2019. Plasticizers, additives that modify the flexibility and rigidity of the product, are ingested as they migrate into food and beverages. Human exposure is continuous and widespread; between 75 and 97% of urine samples contain detectable levels of bisphenols and phthalates, the most common plasticizers. Concern over the toxicity of plasticizers arose in the late 1990s, largely focused around adverse developmental and reproductive effects. More recently, many studies have demonstrated that exposure to plasticizers increases the risk for obesity, type 2 diabetes, and cardiovascular disease (CVD). In the 2000s, many governments including Canada, the United States and European countries restricted the use of certain plasticizers in products targeted towards infants and children. Resultant consumer pressure motivated manufacturers to substitute plasticizers with analogues, which have been marketed as safe. However, data on the effects of these new substitutes are limited and data available to-date suggest that many exhibit similar properties to the chemicals they replaced. The adverse effects of plasticizers have largely been attributed to their endocrine disrupting properties, which modulate hormone signaling. Adipose tissue has been well-documented to be a target of the disrupting effects of both bisphenols and phthalates. Since adipose tissue function is a key determinant of cardiovascular health, adverse effects of plasticizers on adipocyte signaling and function may underlie their link to cardiovascular disease. Herein, we discuss the current evidence linking bisphenols and phthalates to obesity and CVD and consider how documented impacts of these plasticizers on adipocyte function may contribute to the development of CVD.

The enigmatic role of TIPE2 in asthma

2020 ◽  
Vol 319 (1) ◽  
pp. L163-L172
Author(s):  
Bingqing Shi ◽  
Yuqiu Hao ◽  
Wei Li ◽  
Hongna Dong ◽  
Mengting Xu ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Underlying Mechanism ◽  
Cell Receptor ◽  
Asthma Phenotypes ◽  
Downstream Signaling ◽  
Tnf Α ◽  
And Function ◽  
Necrosis Factor

Unlike other members of the tumor necrosis factor (TNF)-α-induced protein 8 (TNFAIP8/TIPE) family that play a carcinogenic role and regulate apoptosis, TNFAIP8-like 2 (TIPE2) can not only maintain immune homeostasis but also regulate inflammation. TIPE2 mainly restrains the activation of T cell receptor (TCR) and Toll-like receptors (TLR), regulating its downstream signaling pathways, thereby regulating inflammation. Interestingly, TIPE2 is abnormally expressed in many inflammatory diseases and may promote or inhibit inflammation in different diseases. This review summarizes the molecular target and cellular function of TIPE2 in immune cells and inflammatory diseases and the underlying mechanism by which TIPE2 regulates inflammation. The function and mechanism of TIPE2 in asthma is also explained in detail. TIPE2 is abnormally expressed in asthma and participates in the pathogenesis of different phenotypes of asthma through regulating multiple inflammatory cells’ activity and function. Considering the indispensable role of TIPE2 in asthma, TIPE2 may be an effective therapeutic target in asthma. However, the available data are insufficient to provide a full understanding of the complex role of TIPE2 in human asthma. Further study is still necessary to explore the possible mechanism and functions of TIPE2 in different asthma phenotypes.

Evaluation of Left Atrial Anatomy and Function using Multidetector Computed Tomography in Patients Undergoing Catheter Ablation for Atrial Fibrillation

2017 ◽  
pp. 39-55 ◽  
Author(s):  
V. I. Gurina ◽  
E. V. Kondrat’ev ◽  
A. Sh. Revishvily ◽  
M. Z. Alimurzaeva
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrium ◽  
Pulmonary Veins ◽  
Systemic Review ◽  
Free Access ◽  
Contrast Enhanced ◽  
Review Reports ◽  
And Function

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Сatheter ablation (CA) of arrhythmogenic foci is supposed to be an established treatment option for symptomatic  patients with AF, refractory to antiarrhythmic therapy. Pre-procedural imaging is indispensable for the assessment of left atrium,  pulmonary veins and adjacent anatomy, and facilitates selection of  the ablation strategy to achieve an optimal result and minimize the risk of complications.Purpose: to evaluate the role of contrast-enhanced MDCT in  patients with AF; also to present the prospects for further  development of this method according to the systemic review of world research data.Materials and methods. 140 free access articles requested as  “MDCT left atrium”, “MDCT pulmonary veins”, “MDCT atrial  appendage” from 01.2009 until 01.2017 were analyzed in PubMed,  as well as a number of Russianlanguage articles in eLibrary.Results.This literature review reports and systematizes available  data on epidemiology and mechanisms of AF, represents current  classification. In addition were analyzed advantages of MDCT over  other methods of visualization while planning the CA and follow-up.Conclusion.MDCT is precise, effective and accessible option, which  satisfies visualization requirements during the preparation for CA.  Moreover, using MDCT in combination with electro-mapping systems  increases safety and effectiveness of the procedure. In postoperative period MDCT can be used for complications diagnostic and results assessment.

Post Translational Modification and its pathologic association in Rheumatoid Arthritis: A brief perspective

2021 ◽  
Vol 22 ◽  
Author(s):  
Vishnupreetha Vasudevan ◽  
Prachi Agnihotri ◽  
Sagarika Biswas
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Pain ◽  
Cyclic Peptide ◽  
Delayed Diagnosis ◽  
Living System ◽  
The Body ◽  
Post Translational Modification ◽  
And Function ◽  
Inflammatory Autoimmune Disease

: Post Translational Modification (PTM) is the process in which covalent addition of functional groups on protein happens to maintain their structure, function and stability. Every PTM process in our living system happens to increase the functional diversity of protein. But sometimes it happens without any regulation and occurrence of this specific change in proteins are leading to autoimmunity. Rheumatoid arthritis (RA) is one such chronic, inflammatory, autoimmune disease that affects joints. Proper treatment can be manageable for RA, but it is not completely curable. Delayed diagnosis of RA can cause severe bone pain, stiffness, inflammation, redness in joints and affect other parts of the body such as liver, kidney etc. Early diagnosis of disease is preferable to cure it effectively. Currently, Rheumatoid factor (RF) and anti-citrullinated cyclic peptide (Anti-CCP) are considered as biomarkers to diagnose RA. Other than citrullination several other PTM’s are also involved in generation of autoantibodies such as, carbamylation, glycosylation, glycation, acetylation, ubiquitination, proteolysis, phosphorylation, lipidation. Aim of this review is to elucidate several considerable changes in form, nature and function of above PTMs in RA, affecting joints and day to day life. This review will give a recent overview on the role of PTMs in the pathogenesis of RA, focusing on the modifications.

Role of hypothermia induced by tumor necrosis factor on apoptosis and function of inflammatory neutrophils in mice

2000 ◽  
Vol 278 (1) ◽  
pp. R157-R165 ◽  
Author(s):  
Toshiko Mizuno ◽  
Yukiko Kannan ◽  
Midori Tokunaga ◽  
Mitsuaki Moriyama ◽  
Yasuo Kiso ◽  
...  
Keyword(s):  
Body Temperature ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Protein Synthesis Inhibitor ◽  
Neutrophil Accumulation ◽  
Tnf Α ◽  
And Function ◽  
Necrosis Factor

Changes in body temperature and cell infiltration, mediated by cytokines including tumor necrosis factor-α (TNF-α), occur during inflammation, but a role of body temperature on inflammatory responses remains obscure. Intraperitoneal injection of 10% casein to mice resulted in transient hypothermia followed by neutrophil accumulation in peritoneal cavities. Peritoneal TNF-α was rapidly raised, and pretreatment of mice with an anti-TNF-α antibody promoted temperature restoration and partially inhibited neutrophil accumulation. To investigate direct effects of body temperature on neutrophils, peritoneal or peripheral blood neutrophils were cultured at 35°C or 37°C with or without recombinant murine TNF-α (100 ng/ml) or a protein synthesis inhibitor cycloheximide (1 μg/ml). Significant inhibition of spontaneous and TNF-α-induced apoptosis was obtained at 35°C compared with 37°C, an effect that was not altered by the addition of cycloheximide. Moreover, phagocytic ability of peritoneal neutrophils was significantly enhanced by incubating them at the lower temperature. These results indicate that mild hypothermia induced by endogenous TNF-α has enhancing roles on neutrophil survival and function during peritoneal inflammation.

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