scholarly journals The Role of Neurohormonal Systems, Inflammatory Mediators and Oxydative Stress in Cardiomyopathy

2021 ◽  
Author(s):  
Ronald Zolty
Keyword(s):  
Oxidative Stress ◽  
Dilated Cardiomyopathy ◽  
Cardiac Remodeling ◽  
Morphological Changes ◽  
Left Ventricular ◽  
Cardiac Inflammation ◽  
Oxydative Stress ◽  
Tnf Α ◽  
Factor Α ◽  
And Function

Cardiomyopathy and more specifically the dilated cardiomyopathy, regardless of severity, is associated with activation of neuro-hormonal, cytokine and oxidative stress signaling pathways that alter the structure and function of cardiac myocytes and non-myocyte cells. These cellular alterations culminate in the morphological changes in cardiac structure termed as cardiac remodeling, a maladaptive process that contributes to further left ventricular dysfunction and heart failure development. This pathological progression is mainly driven by circulating mediators, in particular angiotensin II and norepinephrine. Natriuretic peptides, endothelin-1, vasopressin play also an important role in the progression of the cardiomyopathy. Cardiac inflammation, mediated by cytokines such as tumor necrosis factor-α (TNF-α), interleukins 1 (IL-1) and 6 (IL-6), as well as the oxidative stress were also shown to worsen the cardiac function. Although these pathways have been described separately, they are critically inter-dependent in the response to the development and progression of the dilated cardiomyopathy. This chapter reviews the cellular basis for cardiac remodeling and the mechanisms that contribute to these cellular abnormalities and, more broadly, to the pathophysiology of dilated cardiomyopathy, its progression and its potential treatments.

scholarly journals Comparative and Combinatorial Effects of Resveratrol and Sacubitril/Valsartan alongside Valsartan on Cardiac Remodeling and Dysfunction in MI-Induced Rats

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 5006
Author(s):  
Pema Raj ◽  
Karen Sayfee ◽  
Mihir Parikh ◽  
Liping Yu ◽  
Jeffrey Wigle ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Myocardial Tissue ◽  
Additive Effects ◽  
Sprague Dawley ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Sprague Dawley Rats ◽  
And Function ◽  
Neutrophil Gelatinase

The development and progression of heart failure (HF) due to myocardial infarction (MI) is a major concern even with current optimal therapy. Resveratrol is a plant polyphenol with cardioprotective properties. Sacubitril/valsartan is known to be beneficial in chronic HF patients. In this study, we investigated the comparative and combinatorial benefits of resveratrol with sacubitril/valsartan alongside an active comparator valsartan in MI-induced male Sprague Dawley rats. MI-induced and sham-operated animals received vehicle, resveratrol, sacubitril/valsartan, valsartan alone or sacubitril/valsartan + resveratrol for 8 weeks. Echocardiography was performed at the endpoint to assess cardiac structure and function. Cardiac oxidative stress, inflammation, fibrosis, brain natriuretic peptide (BNP), creatinine and neutrophil gelatinase associated lipocalin were measured. Treatment with resveratrol, sacubitril/valsartan, valsartan and sacubitril/valsartan + resveratrol significantly prevented left ventricular (LV) dilatation and improved LV ejection fraction in MI-induced rats. All treatments also significantly reduced myocardial tissue oxidative stress, inflammation and fibrosis, as well as BNP. Treatment with the combination of sacubitril/valsartan and resveratrol did not show additive effects. In conclusion, resveratrol, sacubitril/valsartan, and valsartan significantly prevented cardiac remodeling and dysfunction in MI-induced rats. The reduction in cardiac remodeling and dysfunction in MI-induced rats was mediated by a reduction in cardiac oxidative stress, inflammation and fibrosis.

Morphological and functional changes in cardiac myocytes isolated from mice overexpressing TNF-α

2003 ◽  
Vol 284 (3) ◽  
pp. H960-H969 ◽  
Author(s):  
Andrzej M. Janczewski ◽  
Toshiaki Kadokami ◽  
Bonnie Lemster ◽  
Carole S. Frye ◽  
Charles F. McTiernan ◽  
...  
Keyword(s):  
Contractile Function ◽  
Left Ventricular ◽  
Mrna Levels ◽  
Functional Changes ◽  
Tnf Α ◽  
Intracellular Ca ◽  
And Gender ◽  
Factor Α ◽  
And Function

Transgenic (TG) TNF1.6 mice, which cardiac specifically overexpress tumor necrosis factor-α (TNF-α), exhibit heart failure (HF) and increased mortality, which is markedly higher in young (<20 wk) males (TG-M) than females (TG-F). HF in this model may be partly caused by remodeling of the extracellular matrix and/or structure/function alterations at the single myocyte level. We studied left ventricular (LV) structure and function using echocardiography and LV myocyte morphometry, contractile function, and intracellular Ca2+ (Ca[Formula: see text]) handling using cell edge detection and fura 2 fluorescence, respectively, in 12-wk-old TG-M and TG-F mice and their wild-type (WT) littermates. TG-F mice showed LV hypertrophy without dilatation and only a small reduction of basal fractional shortening (FS) and response to isoproterenol (Iso). TG-M mice showed a large LV dilatation, higher mRNA levels of β-myosin heavy chain and atrial natriuretic factor versus TG-F mice, reduced FS relative to both WT and TG-F mice, and minimal response to Iso. TG-F and TG-M myocytes were similarly elongated (by ≈20%). The amplitude of Ca[Formula: see text] transients and contractions and the response to Iso were comparable in WT and TG-F myocytes, whereas the time to 50% decline (TD50%) of the Ca[Formula: see text]transient, an index of the rate of sarcoplasmic reticulum Ca2+ uptake, was prolonged in TG-F myocytes. In TG-M myocytes, the amplitudes of Ca[Formula: see text] transients and contractions were reduced, TD50% of the Ca[Formula: see text] transient was prolonged, and the inotropic effect of Iso on Ca[Formula: see text] transients was reduced approximately twofold versus WT myocytes. Protein expression of sarco(endo)plasmic reticulum Ca2+-ATPase 2 and phospholamban was unaltered in TG versus WT hearts, suggesting functional origins of impaired Ca2+ handling in the former. These results indicate that cardiac-specific overexpression of TNF-α induces myocyte hypertrophy and gender-dependent alterations in Ca[Formula: see text] handling and contractile function, which may at least partly account for changes in LV geometry and in vivo cardiac function in this model.

scholarly journals miR155 Deficiency Reduces Myofibroblast Density but Fails to Improve Cardiac Function after Myocardial Infarction in Dyslipidemic Mouse Model

2021 ◽  
Vol 22 (11) ◽  
pp. 5480
Author(s):  
David Schumacher ◽  
Adelina Curaj ◽  
Sakine Simsekyilmaz ◽  
Andreas Schober ◽  
Elisa A. Liehn ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Mouse Model ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Cardiac Inflammation ◽  
Infarction Size ◽  
Adverse Remodeling ◽  
And Function

Myocardial infarction remains the most common cause of heart failure with adverse remodeling. MicroRNA (miR)155 is upregulated following myocardial infarction and represents a relevant regulatory factor for cardiac remodeling by engagement in cardiac inflammation, fibrosis and cardiomyocyte hypertrophy. Here, we investigated the role of miR155 in cardiac remodeling and dysfunction following myocardial infarction in a dyslipidemic mouse model. Myocardial infarction was induced in dyslipidemic apolipoprotein E-deficient (ApoE−/−) mice with and without additional miR155 knockout by ligation of the LAD. Four weeks later, echocardiography was performed to assess left ventricular (LV) dimensions and function, and mice were subsequently sacrificed for histological analysis. Echocardiography revealed no difference in LV ejection fractions, LV mass and LV volumes between ApoE−/− and ApoE−/−/miR155−/− mice. Histology confirmed comparable infarction size and unaltered neoangiogenesis in the myocardial scar. Notably, myofibroblast density was significantly decreased in ApoE−/−/miR155−/− mice compared to the control, but no difference was observed for total collagen deposition. Our findings reveal that genetic depletion of miR155 in a dyslipidemic mouse model of myocardial infarction does not reduce infarction size and consecutive heart failure but does decrease myofibroblast density in the post-ischemic scar.

scholarly journals Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3573
Author(s):  
Lian-Chun Li ◽  
Zheng-Hong Pan ◽  
De-Sheng Ning ◽  
Yu-Xia Fu
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Morphological Changes ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase ◽  
Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

scholarly journals Vitamin D Status in Children with Idiopathic Dilated Cardiomyopathy

2021 ◽  
Vol 11 (01) ◽  
pp. e120-e124
Author(s):  
Duaa M. Raafat ◽  
Osama M. EL-Asheer ◽  
Amal A. Mahmoud ◽  
Manal M. Darwish ◽  
Naglaa S. Osman
Keyword(s):  
Vitamin D ◽  
Serum Level ◽  
Dilated Cardiomyopathy ◽  
Smooth Muscles ◽  
Left Ventricular ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Vitamin D Receptors ◽  
Left Ventricular Dimensions ◽  
And Function ◽  
Ventricular Dimensions

AbstractDilated cardiomyopathy (DCM) is the third leading cause of heart failure in pediatrics. The exact etiology of DCM is unknown in more than half of the cases. Vitamin D receptors are represented in cardiac muscles, endothelium, and smooth muscles of blood vessels suggesting that vitamin D could have a vital cardioprotective function. This study aimed to assess serum level of vitamin D in children with idiopathic DCM and to correlate the serum level of vitamin D with the left ventricular dimensions and function. This study is a descriptive cross-sectional single-center study, includes 44 children of both sexes, diagnosed as idiopathic DCM. Serum level of vitamin D was assessed and correlated with the left ventricular dimensions and function. Mean age of studied children was 6.08 ± 4.4 years. Vitamin D deficiency was found in 90.9% of children with idiopathic DCM with a mean level 13.48 ng/mL. There was a negative correlation between vitamin D level and fraction shortening and left ventricular end-diastolic diameter in children with DCM. Vitamin D level is not only significantly low in children with idiopathic DCM but it is also significantly correlated with the degree of left ventricular dysfunction.

Abstract MP216: Identification Of Novel Phosphoprotein Signaling Pathways In Human Dilated Cardiomyopathy By Integrative Proteomic And Phosphoproteomic Analysis

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Cristine J Reitz ◽  
Marjan Tavassoli ◽  
Da Hye Kim ◽  
Sina Hadipour-Lakmehsari ◽  
Saumya Shah ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Cardiac Tissue ◽  
Regulatory Element ◽  
Critical Role ◽  
Left Ventricular ◽  
Confocal Imaging ◽  
Intercalated Disc ◽  
Bioinformatics Analyses ◽  
Tissue Samples ◽  
And Function

Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure, yet the majority of the underlying signaling mechanisms remain poorly characterized. Protein phosphorylation is a key regulatory element with profound effects on the activity and function of signaling networks; however, there is a lack of comprehensive phosphoproteomic studies in human DCM patients. We assessed the hypothesis that an integrative phosphoproteomics analysis of human DCM would reveal novel phosphoprotein candidates involved in disease pathophysiology. Combined proteomic and phosphoproteomic analysis of explanted left ventricular tissue samples from DCM patients ( n =4) and non-failing controls ( n =4) identified 5,570 unique proteins with 13,624 corresponding phosphorylation sites. From these analyses, we identified αT-catenin as a unique candidate protein with a cluster of 4 significantly hyperphosphorylated sites in DCM hearts ( P <0.0001), with no change in total αT-catenin expression at the protein level. Bioinformatics analyses of human datasets and confocal imaging of human and mouse cardiac tissue show highly cardiac-enriched expression of αT-catenin, localized to the cardiomyocyte intercalated disc. High resolution 3-dimensional reconstruction shows elongated intercalated disc morphology in DCM hearts (10.07±0.76 μm in controls vs. 17.20±1.87 μm in DCM, P <0.05, n =3/group), with significantly increased colocalization of αT-catenin with the intercalated disc membrane protein N-cadherin (Pearson’s coefficient 0.55±0.04 in controls vs. 0.71±0.02 in DCM, P <0.05, n =3/group). To investigate the functional role of cardiac αT-catenin phosphorylation, we overexpressed WT protein vs. non-phosphorylatable forms based on the loci identified in DCM hearts, in adult mouse cardiomyocytes using lentiviral transduction. Confocal imaging revealed significant internalization of the phospho-null form, as compared to the prominent intercalated disc staining of the WT protein (17.78±0.79% of WT vs. 9.25±0.49% of 4A mutant, P <0.0001, n =50 cells/group). Together, these findings suggest a critical role for αT-catenin phosphorylation in maintaining cardiac intercalated disc organization in human DCM.

Abstract 999: Gated Micro Computed Tomography Scanning: An Emerging Tool for Longitudinal Assessment of Murine Cardiac Remodeling.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Ahmad Y Sheikh ◽  
Timothy C Doyle ◽  
Maryam K Sheikh ◽  
Feng Cao ◽  
Katherine J Ransohoff ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Cardiac Remodeling ◽  
High Energy ◽  
Left Ventricular ◽  
Structure And Function ◽  
Coronary Artery Ligation ◽  
Micro Ct ◽  
Ventricular Ejection Fraction ◽  
Computed Tomography Scanning ◽  
And Function

Background: Recent advances in high energy X-ray source computed tomography (CT) technology have made it possible to accurately image murine cardiac structure and function. We describe the use of a gated Micro CT system to assess cardiac remodeling in a murine model of myocardial infarction (MI). Methods: Adult FVB mice (n = 10) were randomized to surgically induced MI by left coronary artery ligation or sham procedure. Dual gated cardiac and respiratory Micro CT scans were performed pre-operatively and at weeks 4, 8 and 12 post-procedure. End-diastolic and end-systolic images were acquired by gating on the ECG P-and S’-waves, respectively. Post-acquisition analysis was performed using image analysis software and the following parameters were quantified: left ventricular (LV) volume and mass, right ventricular volume and mass, right and left atrial volumes, and ventricular ejection fraction (EF). Results: Images were successfully acquired with a resolution of 100 microns allowing for identification and quantification of key cardiac structures (Fig 1A ). Following MI, animals exhibited left ventricular failure with significantly increased* end systolic and diastolic volumes by week 4. Ventricular dilation continued through week 8, plateauing by week 12. Left ventricular mass increased steadily over 12 weeks*, with a significantly decreased* LVEF of 28.0 ± .05% by week 12 (pre-MI: 66.7 ± .06%,*p < 0.01). Post-MI left ventricular change is detailed in Fig 1B . Conclusions: MicroCT scanning can be successfully used to characterize murine myocardial structure and function, making it a useful tool to assess cardiac phenotypes and models of cardiovascular disease.

The Role of Oxidative Stress, Inflammation, and Advanced Glycation End Product in Skin Manifestations of Diabetes Mellitus

2021 ◽  
Vol 17 ◽  
Author(s):  
Lili Legiawati
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Skin Disorders ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
High Level ◽  
Factor Α

: Diabetes mellitus is a metabolic disorder caused by an increase in insulin resistance, a decrease in insulin production, or both of them, resulting in a high level of blood glucose or hyperglycemia. An uncontrolled state of DM may cause complications, namely skin disorder. One or more skin disorders are found amongst 74% of T2DM patients, with the highest percentage is dry skin (47%), followed by infection (10%), diabetic hand (5%), hair loss and diabetic dermopathy (each 4%). In DM, the state of hyperglycemia and production of advanced glycaemic end-products (AGEs) profoundly impact skin changes. In the pathological pathway, AGEs induce oxidative stress and inflammation. Nonetheless, AGEs level is higher in T2DM patients compared to non-T2DM people. This is caused by hyperglycemia and oxidative stress. Binding between AGEs and receptor of AGEs (RAGE) promotes pathway of oxidative stress and inflammation cascade via mitogen-activated protein kinases (MAPK), nuclear factor-k-light-chain-enhancer of activated β cells (NF-kβ), interleukin- 6 (IL-6), tumor necrosis factor-α (TNF-α), expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 2 (VCAM-2) pathway which furtherly effectuates DM complication including skin disorders.

scholarly journals Andrographis paniculata and Its Bioactive Diterpenoids Against Inflammation and Oxidative Stress in Keratinocytes

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 530 ◽  
Author(s):  
Eugenie Mussard ◽  
Sundy Jousselin ◽  
Annabelle Cesaro ◽  
Brigitte Legrain ◽  
Eric Lespessailles ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Quantitative Polymerase Chain Reaction ◽  
Andrographis Paniculata ◽  
Ros Production ◽  
Inflammatory Conditions ◽  
Tnf Α ◽  
Dichlorofluorescein Diacetate ◽  
Polymerase Chain ◽  
Factor Α ◽  
Necrosis Factor

Andrographis paniculata was widely used in traditional herbal medicine to treat various diseases. This study explored the potential anti-aging activity of Andrographis paniculata in cutaneous cells. Human, adult, low calcium, high temperature (HaCaT) cells were treated with methanolic extract (ME), andrographolide (ANDRO), neoandrographolide (NEO), 14-deoxyandrographolide (14DAP) and 14-deoxy-11,12-didehydroandrographolide (14DAP11-12). Oxidative stress and inflammation were induced by hydrogen peroxide and lipopolysaccharide/TNF-α, respectively. Reactive oxygen species (ROS) production was measured by fluorescence using a 2′,7′-dichlorofluorescein diacetate (DCFH-DA) probe and cytokines were quantified by ELISA for interleukin-8 (IL-8) or reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for tumor necrosis factor-α (TNF-α). Hyaluronic acid (HA) secretion was determined by an ELISA. Our results show a decrease in ROS production and TNF-α expression by ME (5 µg/mL) in HaCaT under pro-oxidant and pro-inflammatory conditions, respectively. ME protected HaCaT against oxidative stress and inflammation. Our findings confirm that ME can be used for the development of bioactive compounds against epidermal damage.

Oxidative stress-induced cell death of human oral neutrophils

2003 ◽  
Vol 284 (4) ◽  
pp. C1048-C1053 ◽  
Author(s):  
Eisuke F. Sato ◽  
Masahiro Higashino ◽  
Kazuo Ikeda ◽  
Ryotaro Wake ◽  
Mitsuyoshi Matsuo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Caspase 3 ◽  
Nuclear Dna ◽  
Kinase Inhibitor ◽  
Tissue Injury ◽  
Morphological Changes ◽  
Limited Information ◽  
And Function

Polymorphonuclear leukocytes (PMN) play crucial roles in protecting hosts against invading microbes and in the pathogenesis of inflammatory tissue injury. Although PMN migrate into mucosal layers of digestive and respiratory tracts, only limited information is available of their fate and function in situ. We previously reported that, unlike circulating PMN (CPMN), PMN in the oral cavity spontaneously generate superoxide radical and nitric oxide (NO) in the absence of any stimuli. When cultured for 12 h under physiological conditions, oral PMN (OPMN) showed morphological changes that are characteristic of those of apoptosis. Upon agarose gel electrophoresis, nuclear DNA samples isolated from OPMN revealed ladder-like profiles characteristic of nucleosomal fragmentation.l-cysteine, reduced glutathione (GSH), and herbimycin A, a protein tyrosine kinase inhibitor, suppressed the activation of caspase-3 and apoptosis of OPMN. Neither thiourea, superoxide dismutase (SOD), nor catalase inhibited the activation of caspase-3 and apoptosis. Moreover, N-acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO), inhibitor for caspase-3, inhibited the fragmentation of DNA. These results suggested that oxidative stress and/or tyrosine-kinase-dependent pathway(s) activated caspase-3 in OPMN, thereby inducing their apoptosis.

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