Changes in Expressions of HSP27, HSP70 and Soluble Glycoprotein in Heart Failure Rats Complicated with Pulmonary Edema and Correlations with Cardiopulmonary Functions Running title: Expressions of HSP27, HSP70 and Soluble Glycoprotein in Heart Failure

2021 ◽  
Vol 7 (5) ◽  
pp. 4286-4295
Author(s):  
Yan Tan ◽  
Bo Gao ◽  
Dongming Gu ◽  
Shuyun Wang ◽  
Zhinua Wang
Keyword(s):  
Heart Failure ◽  
Protein Expression ◽  
Pulmonary Edema ◽  
Airway Resistance ◽  
Lung Compliance ◽  
Left Ventricular ◽  
Normal Group ◽  
Model Group ◽  
Expression Levels ◽  
Gene And Protein Expression

Objective: The study aimed to investigate the changes in expressions of heat shock protein 27 (HSP27), HSP70 and soluble glycoprotein (SGP) in heart failure (HF) rats complicated with pulmonary edema, and explore their potential correlations with cardiopulmonary functions. Methods: The rat model of HF was established, and the rats were divided into HF model group (model group, n=15) and normal group (n=15). After successful modeling, MRI and ECG were applied to detect the cardiac function indexes of the rats. The myocardial function indexes were determined, the injury of myocardial tissues was observed via hematoxylin and eosin (HE) staining, and the content of myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-alpha (TNF-a) in the blood was measured. The partial pressure of oxygen (Pa02) and oxygenation index (01) were observed, and the airway resistance and lung compliance were examined. Moreover, quantitative polymerase chain reaction (qPCR) and Western blotting assay were performed to detect the gene and protein expression levels of HSP27, HSP70 and SGP130. Results: The levels of serum creatine kinase (CK), creatine (Cr) and blood urea nitrogen (BUN) were increased markedly in model group (p<0.05). Model group had notably decreased fractional shortening (FS) and ejection fraction (EF) compared with normal group (p<0.05), while the opposite results of left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were detected. In model group, the content of serum MPO, MMP-9 and TNF-a was raised remarkably (p<0.05), 01 and Pa02were reduced notably (p<0.05), the airway resistance was increased (p<0.05), and the lung compliance was decreased (p<0.05). Obviously elevated gene and protein expression levels of HSP27, HSP70 and SGP130 were detected in model group (p<0.05). Conclusion: The expressions of HSP27, HSP70 and SGP130 are increased in HF rats complicated with pulmonary edema, seriously affecting the cardiopulmonary functions of the rats.

Abstract 417: Cardiac Akap12 Signalosome Overexpression Exacerbation of Heart Failure and β-arrestin Signaling Pathway

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Hanan Qasim ◽  
Arfaxad Reyes Alcaraz ◽  
Bradley K McConnell
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Systolic Function ◽  
Left Ventricular ◽  
Control Groups ◽  
Expression Levels ◽  
Anchoring Protein ◽  
The Impact

Background: Heart failure (HF) is responsible for 1 out of 8 deaths per year in the U.S.A. andis the major cause of death globally. In HF, chronic β-adrenergic receptor (β-AR)stimulation leads to reduced cardiac function due in part to β-AR desensitization.β-arrestins are proteins that play a major role in desensitizing G protein-coupledreceptors (GPCRs) such as β-AR. Previously we reported enhanced cardiacfunction in mice lacking functional A Kinase Anchoring Protein 12 (AKAP12). Inthis study, we aim to investigate the impact of AKAP12 overexpression(oxAKAP12) on HF progression through assessing β-arrestins. Our central hypothesis is that cardiac AKAP12 overexpression potentiates HF developmentby influencing β-arrestin signaling downstream of the β-AR. Methods: HF was developed in WT and oxAKAP12-Tg mice (8-10) weeks old males andfemales, through chronic Isoproterenol (ISO) administration (60mg/kg/day for 14days). Left ventricular homogenates were used for gene expression analysis.Furthermore, AKAP12 was transiently overexpressed in AC16 cells (humancardiomyocytes cell line), to asses protein expression levels and Gαs pathwayactivity, upon treatment with 100 nM of ISO. Results: Cardiac oxAKAP12 in both males and females reduced left ventricular ejectionfraction (EF) by 14.5±2.5% and fractional shortening (FS) by 22.7±2% after 14-days of chronic ISO treatment when compared to control groups. β-arrestin-1gene expression levels were significantly lower (p=0.022) in oxAKAP12 malehomogenates treated with ISO (14 days) compared to control groups.Interestingly, female homogenates overexpressing AKAP12 showed significantlyhigher β-arrestin-1 gene expression levels (p<0.0001) with ISO treatment,compared to control groups. In AC16 cells overexpressing AKAP12 and treatedwith ISO, Gαs activity and β-arrestin-1 protein expression levels were bothreduced by 50% compared to AC16 ISO treated groups. Conclusion: Cardiac oxAKAP12 negatively influences systolic function in both male andfemale mice, potentially through affecting β-arrestin signaling pathway. Thus,designing novel drugs to inhibit AKAP12 is promising to ameliorate HF.

Combination of Huangqi Granule and Rosuvastatin Improves the Cardiac Function in Heart Failure

2020 ◽  
Vol 19 (2) ◽  
pp. 181-187
Author(s):  
Jing Li ◽  
Yun Zhang ◽  
Weizhong Huangfu ◽  
Yuhong Ma
Keyword(s):  
Heart Failure ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Wall Thickness ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Model Group ◽  
Ventricular Ejection Fraction ◽  
Posterior Wall Thickness

Using rat models of heart failure, we evaluated the effects of rosuvastatin and Huangqi granule alone and in combination on left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole, and left ventricular posterior wall thickness at end-systole. Results showed that left ventricular end-diastolic dimension, left ventricular end-systolic dimension in the rosuvastatin + Huangqi granule group were significantly decreased (P ‹ 0.01), while left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole and left ventricular posterior wall thickness at end-systole were significantly increased (P ‹ 0.05). The serum IL-2, IFN-β, and TNF-α in rosuvastatin + Huangqi granule group were significantly lower than those in model group (P ‹ 0.05). However, the levels of S-methylglutathione and superoxide dismutase in rosuvastatin + Huangqi granule group were significantly higher, while nitric oxide was significantly lower than that in the model group (P ‹ 0.05). Also, compared to the model group, the apoptosis rate, and the autophagy protein LC3-II in the cardiomyocytes of rosuvastatin + Huangqi granule group was significantly decreased (P ‹ 0.01), while the level of p62 protein was significantly increased (P ‹ 0.01). The levels of AMPK and p-AMPK in cardiomyocytes were significantly lower in rosuvastatin + Huangqi granule group; however, the levels of mTOR and p-mTOR showed an opposite trend (P ‹ 0.05). To sum up, rosuvastatin + Huangqi granule could improve the cardiac function, decrease the level of oxidative stress, and inflammatory cytokines in rats with HF. The possible underlying mechanism might be inhibition of autophagy and reduced apoptosis in cardiomyocytes by regulating AMPK-mTOR signaling pathway.

Abstract 399: End-stage Heart Failure Causes Severe Lung Fibrosis and Dysfunction

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Xiaohong Liu ◽  
Huan Wang ◽  
Ruru Shang ◽  
Jin Zhang ◽  
Yingjie Chen
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Lung Fibrosis ◽  
Smooth Muscles ◽  
Lung Compliance ◽  
Left Ventricular ◽  
Lung Weight ◽  
Lung Dysfunction ◽  
Lv Ejection Fraction ◽  
End Stage

Chronic heart failure (CHF) causes trouble breathing in patients. We recently demonstrated that systolic pressure overload by transverse aortic constriction (TAC) causes severe left ventricular (LV) failure that is associated with massive lung fibrosis and lung vascular remodeling, and right ventricular (RV) dysfunction in mice. Here, we further studied the effect of CHF on lung structure and function in mice, and the effect of CHF on lung fibrosis in patients. We demonstrated that chronic TAC resulted in decrease of LV ejection fraction, and increases LV weight, lung weight, and RV weight, as well as their ratios to bodyweight. Interestingly, the development of LV failure is associated with a significant lung dysfunction as evidenced by a ~2-fold increase of lung resistance and a ~50% dramatic decrease of lung compliance in vivo . Lung compliance was also significantly reduced ~50% in lung isolated from CHF mice, indicating the decrease of lung compliance is due to the structure change of lung. The reduced lung compliance in CHF mice is significantly correlated with the decrease of LV ejection fraction, the increase of lung weight, and RV hypertrophy, suggesting the reduced lung compliance might contribute to the development of RV hypertrophy and failure. Histochemical analyses further demonstrated that CHF causes massive lung vascular, perivascular and interstitial fibrosis, as well as increase of lung myofibroblast proliferation. By using the chimeric mice created by transplantation of Bone Marrow Derived Cells (BMDCs) from GFP mice into wild type mice, we demonstrated that BMDCs contribute to the increased lung myofibroblasts and lung fibrosis. However, BMDCs don’t differentiate into lung smooth muscles cells in CHF mice. Moreover, we demonstrated that inhibition of lung inflammation by a cytokine therapy protocol is effective in attenuating TAC-induced lung fibrosis. Finally, we demonstrated that end-stage CHF causes increase of lung fibrosis in patients, and the increased lung fibrosis is associated with RV hypertrophy and dysfunction in patients. Together, our study demonstrated that end-stage CHF causes lung fibrosis and lung dysfunction, and inhibition of inflammation is effective in attenuating heart failure induced lung fibrosis.

Abstract 151: A Novel Role for DDiT4L in Regulation of mTOR and Autophagy in the Heart

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Bridget Simonson ◽  
Hannabeth Franchino ◽  
Ashley Knight ◽  
Anthony Rosenzweig ◽  
Saumya Das
Keyword(s):  
Heart Failure ◽  
Protein Expression ◽  
Glucose Deprivation ◽  
Mtor Signaling ◽  
Confocal Imaging ◽  
Negative Regulator ◽  
Neonatal Rat ◽  
Pathological Hypertrophy ◽  
Gene And Protein Expression ◽  
Physiological Hypertrophy

Introduction: DDiT4L is a known negative regulator of mTOR signaling in skeletal muscle; however its role in the heart is unknown. We have recently showed increased DDiT4L mRNA in a murine transgenic model of pathological but not physiological hypertrophy. Here we test the hypothesis that DDiT4L is a regulator of mTOR signaling in the heart and may play a role in pathological hypertrophy and heart failure. Methods: We investigated the regulation of DDiT4L in murine models of hypertrophy and in cultured neonatal rat ventricular cardiomyocytes (NRVMs). Loss and gain of function of DDiT4L in mTOR regulation and autophagy was investigated using confocal imaging, immunoblotting, and qRT-PCR in NRVMs. Results: DDiT4L gene and protein expression was increased four-fold in pressure overload hypertrophy (n = 4-6, p<0.001), but not in a swim model of physiological hypertrophy. DDiT4L gene expression also significantly increased in a genetic model of dilated cardiomyopathy model (n = 4, p<0.001). In NRVMs, DDiT4L was induced by cardiac stressors such as pathological stretch, hypoxia, and glucose deprivation (n = 3-5 in duplicate, p<0.05-0.01). Increased DDiT4L expression correlated with inhibition of mTOR signaling, and an increase in autophagy markers. siRNA ablation of DDiT4L revealed that inhibition of mTOR signaling by DDiT4L was necessary for glucose deprivation induced autophagy, as determined by imaging of GFP-LC3 autophagosomes (n = 3 in duplicate, p<0.01), and immunoblotting of autophagy markers. Conversely, adenoviral-driven overexpression of DDiT4L inhibited mTOR signaling and significantly increased basal autophagy (n = 3 in duplicate, p<0.05). In TAC mice, the increase in DDiT4L protein expression correlated to inhibition of mTOR signaling, increases in autophagy markers (p<0.01), and preceded the transition to LV dilation and HF. Conclusion: Our data suggests that DDiT4L expression is altered in diverse models of pathological hypertrophy and precedes the development of LV dilatation and overt heart failure. DDiT4L inhibition of mTOR and modulation of autophagy may play a role in the progression to heart failure. DDiT4L may represent a novel therapeutic target to prevent this transition.

scholarly journals Diagnostic impact of promoter methylation and E-cadherin gene and protein expression levels in laryngeal carcinoma

2013 ◽  
Vol 3 ◽  
pp. 263-271
Author(s):  
Katarzyna Starska ◽  
Ewa Forma ◽  
Iwona Lewy-Trenda ◽  
Paweł Papież ◽  
Jan Woś ◽  
...  
Keyword(s):  
Protein Expression ◽  
Promoter Methylation ◽  
Laryngeal Carcinoma ◽  
Expression Levels ◽  
Diagnostic Impact ◽  
Gene And Protein Expression ◽  
E Cadherin

scholarly journals Effect of Shenfu Qiangxin on the expression of TGF-β/Smads signaling pathway-related molecules in myocardium of rats with heart failure

2019 ◽  
Vol 17 ◽  
pp. 205873921985285
Author(s):  
Li Xiong ◽  
Guobo Xie ◽  
Binhua Luo ◽  
Zhiliang Mei
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Signaling Pathway ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Tgf Beta ◽  
Model Group ◽  
Ventricular Ejection Fraction ◽  
Tnf Α ◽  
Losartan Group

This study aims to evaluate the effect of Shenfu Qiangxin on TGF-β/Smads signaling pathway-related molecules in myocardial tissue of rats with heart failure. Five rats were selected as sham-operated group, while another 15 rats with heart failure were divided into three groups, including model group, losartan group, and Shenfu Qiangxin group. Rats in losartan group were given losartan intragastric intervention, the rats in Shenfu Qiangxin group were given Shenfu Qiangxin mixture intervention, while rats in another two groups were given equal volume of sterile saline intervention. During the treatment, the levels of B-type brain natriuretic peptide (BNP), lactate dehydrogenase (LDH), free fatty acids (FFA), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and TGF-β/Smads signaling pathway were measured in rats. Compared with model group, the expression of ejection fraction (EF), left ventricular ejection fraction (LVSP), TGF-β 1, Smad2, and Smad3 significantly decreased in sham-operated group, losartan group, and Shenfu Qiangxin group, while left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVDd), left ventricular end-diastolic pressure (LVEDP), BNP, LDH, FFA, TNF-α, and IL-6 levels increased ( P < 0.05). Compared with sham-operated group, the expression of EF, LVSP, TGF-beta 1, Smad2, and Smad3 dramatically decreased in losartan group, Shenfu Qiangxin group, but LVEDV, LVDd, LVEDP, BNP, LDH, FFA, TNF-α, and IL-6 levels increased ( P < 0.05). Compared with losartan group, the expression of EF, LVSP, TGF-beta 1, Smad2, and Smad3 upregulated in Shenfu Qiangxin group, while LVEDV, LVDd, LVEDP, BNP, LDH, FFA, TNF-α, and IL-6 levels downregulated ( P < 0.05). Consequently, Shenfu Qiangxin could effectively improve the heart function of rats with heart failure, and play an anti-heart failure role by regulating the expression of related molecules of TGF-β/Smads signaling pathway.

Volume overload heart failure: length-tension curves, and response to beta-agonists, Ca2+, and glucagon

1978 ◽  
Vol 235 (6) ◽  
pp. H690-H700
Author(s):  
W. H. Newman
Keyword(s):  
Heart Failure ◽  
Volume Overload ◽  
Left Ventricular ◽  
Normal Group ◽  
Response Curves ◽  
Beta Agonists ◽  
Inotropic Drugs ◽  
Generating Capacity ◽  
Anesthetized Dogs ◽  
Tension Curves

Left ventricular force-generating capacity was determined in 19 anesthetized dogs with heart failure (HF) from aortocaval fistula. At the time of study all dogs had ascites, edema, and elevated pulmonary wedge pressure. Length-contractile force (CF) curves recorded from the left ventricle (LV) with a modified Walton-Brodie arch indicated that the LV was operating on the ascending limb of the length-CF curve at 62.4 +/- 0.1% Lmax in the normal group and in the HF group at 83.4 +/- 2.7% Lmax. In HF the length-CF curve was depressed when compared to normal and was further depressed when CF in grams was normalized for changes in LV wall thickness and expressed as g/cm2. Additionally, dose-response curves of CF in response to injected norepinephrine, isoproterenol, glucagon, and calcium were depressed when compared to the normal group while the response of heart rate and blood pressure was not different. These findings indicate that volume overload HF is associated with depressed ventricular muscle function and a depressed response to inotropic drugs.

scholarly journals Epigenetic regulation of somatostatin and somatostatin receptors in neuroendocrine tumors and other types of cancer

2020 ◽  
Author(s):  
M.J. Klomp ◽  
S.U. Dalm ◽  
M. de Jong ◽  
R.A. Feelders ◽  
J. Hofland ◽  
...  
Keyword(s):  
Protein Expression ◽  
Neuroendocrine Tumors ◽  
Epigenetic Regulation ◽  
Somatostatin Receptors ◽  
Secretory Activity ◽  
Expression Levels ◽  
Epigenetic Machinery ◽  
Gene And Protein Expression

Abstract Both somatostatin (SST) and somatostatin receptors (SSTRs) are proteins with important functions in both physiological tissue and in tumors, particularly in neuroendocrine tumors (NETs). NETs are frequently characterized by high SSTRs expression levels. SST analogues (SSAs) that bind and activate SSTR have anti-proliferative and anti-secretory activity, thereby reducing both the growth as well as the hormonal symptoms of NETs. Moreover, the high expression levels of SSTR type-2 (SSTR2) in NETs is a powerful target for therapy with radiolabeled SSAs. Due to the important role of both SST and SSTRs, it is of great importance to elucidate the mechanisms involved in regulating their expression in NETs, as well as in other types of tumors. The field of epigenetics recently gained interest in NET research, highlighting the importance of this process in regulating the expression of gene and protein expression. In this review we will discuss the role of the epigenetic machinery in controlling the expression of both SSTRs and the neuropeptide SST. Particular attention will be given to the epigenetic regulation of these proteins in NETs, whereas the involvement of the epigenetic machinery in other types of cancer will be discussed as well. In addition, we will discuss the possibility to target enzymes involved in the epigenetic machinery to modify the expression of the SST-system, thereby possibly improving therapeutic options.

scholarly journals Proinflammatory and Anti-Inflammatory Cytokines Mediated by NF-κB Factor as Prognostic Markers in Mammary Tumors

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Gustavo Rodrigues Martins ◽  
Gabriela Bottaro Gelaleti ◽  
Marina Gobbe Moschetta ◽  
Larissa Bazela Maschio-Signorini ◽  
Debora Ap. Pires de Campos Zuccari
Keyword(s):  
Protein Expression ◽  
Survival Time ◽  
Inflammatory Cytokines ◽  
Prognostic Markers ◽  
Tumor Development ◽  
Mammary Tumors ◽  
Clinicopathological Characteristics ◽  
Expression Levels ◽  
Gene And Protein Expression ◽  
High Gene

Inflammation results in the production of cytokines, such as interleukin- (IL-) 4 and IL-10 with immunosuppressive properties or IL-6 and TNF-αwith procarcinogenic activity. Furthermore, NF-κB is the major link between inflammation and tumorigenesis. This study verified the interaction between active inflammatory cytokines in the tumor microenvironment and serum of female dogs with mammary tumors and their correlation with the clinicopathological characteristics and overall survival. Measurement of gene expression was performed by qPCR and protein levels by ELISA/Luminex. High gene and protein expression levels of NF-κB, IL-6, and TNF-αwere found in association with characteristics that reflect worse prognosis and a negative correlation between TNF-αprotein expression and survival time was observed (p<0.05). In contrast, high gene and protein expression levels of IL-4 and IL-10 were associated with characteristics of better prognosis and an increased level of IL-4 and a longer survival time of animals were obtained (p<0.05). In addition, there was a positive correlation between TNF-αand IL-6 expression in association with NF-κB. The results show a significant correlation of these cytokines with tumor development, associated with NF-κB expression and cytokines promodulation, showing that these biological factors could be used as predictive and prognostic markers in breast cancer.

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