scholarly journals Deciphering the Protein, Modular Connections and Precision Medicine for Heart Failure With Preserved Ejection Fraction and Hypertension Based on TMT Quantitative Proteomics and Molecular Docking

2021 ◽  
Vol 12 ◽  
Author(s):  
Guofeng Zhou ◽  
Jiye Chen ◽  
Chuanhong Wu ◽  
Ping Jiang ◽  
Yongcheng Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Immune Response ◽  
Molecular Docking ◽  
Energy Metabolism ◽  
Quantitative Proteomics ◽  
Myocardial Contraction ◽  
Prednisolone Acetate ◽  
Preserved Ejection Fraction ◽  
Functional Connections

Background: Exploring the potential biological relationships between heart failure with preserved ejection fraction (HFpEF) and concomitant diseases has been the focus of many studies for the establishment of personalized therapies. Hypertension (HTN) is the most common concomitant disease in HFpEF patients, but the functional connections between HFpEF and HTN are still not fully understood and effective treatment strategies are still lacking.Methods: In this study, tandem mass tag (TMT) quantitative proteomics was used to identify disease-related proteins and construct disease-related networks. Furthermore, functional enrichment analysis of overlapping network modules was used to determine the functional similarities between HFpEF and HTN. Molecular docking and module analyses were combined to identify therapeutic targets for HFpEF and HTN.Results: Seven common differentially expressed proteins (co-DEPs) and eight overlapping modules were identified in HFpEF and HTN. The common biological processes between HFpEF and HTN were mainly related to energy metabolism. Myocardial contraction, energy metabolism, apoptosis, oxidative stress, immune response, and cardiac hypertrophy were all closely associated with HFpEF and HTN. Epinephrine, sulfadimethoxine, chloroform, and prednisolone acetate were best matched with the co-DEPs by molecular docking analyses.Conclusion: Myocardial contraction, energy metabolism, apoptosis, oxidative stress, immune response, and cardiac hypertrophy were the main functional connections between HFpEF and HTN. Epinephrine, sulfadimethoxine, chloroform, and prednisolone acetate could potentially be effective for the treatment of HTN and HFpEF.

scholarly journals Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in heart failure patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takashi Yokota ◽  
Shintaro Kinugawa ◽  
Kagami Hirabayashi ◽  
Mayumi Yamato ◽  
Shingo Takada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Aerobic Capacity ◽  
Plantar Flexion ◽  
Exercise Intolerance ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Systemic Oxidative Stress

AbstractOxidative stress plays a role in the progression of chronic heart failure (CHF). We investigated whether systemic oxidative stress is linked to exercise intolerance and skeletal muscle abnormalities in patients with CHF. We recruited 30 males: 17 CHF patients, 13 healthy controls. All participants underwent blood testing, cardiopulmonary exercise testing, and magnetic resonance spectroscopy (MRS). The serum thiobarbituric acid reactive substances (TBARS; lipid peroxides) were significantly higher (5.1 ± 1.1 vs. 3.4 ± 0.7 μmol/L, p < 0.01) and the serum activities of superoxide dismutase (SOD), an antioxidant, were significantly lower (9.2 ± 7.1 vs. 29.4 ± 9.7 units/L, p < 0.01) in the CHF cohort versus the controls. The oxygen uptake (VO2) at both peak exercise and anaerobic threshold was significantly depressed in the CHF patients; the parameters of aerobic capacity were inversely correlated with serum TBARS and positively correlated with serum SOD activity. The phosphocreatine loss during plantar-flexion exercise and intramyocellular lipid content in the participants' leg muscle measured by 31phosphorus- and 1proton-MRS, respectively, were significantly elevated in the CHF patients, indicating abnormal intramuscular energy metabolism. Notably, the skeletal muscle abnormalities were related to the enhanced systemic oxidative stress. Our analyses revealed that systemic oxidative stress is related to lowered whole-body aerobic capacity and skeletal muscle dysfunction in CHF patients.

scholarly journals Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Gα oxidation

2020 ◽  
Author(s):  
Detmar Kolijn ◽  
Steffen Pabel ◽  
Yanna Tian ◽  
Mária Lódi ◽  
Melissa Herwig ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Linear Regression Analysis ◽  
Lipid Peroxide ◽  
Dependent Manner ◽  
Preserved Ejection Fraction ◽  
Human Heart Failure ◽  
Stress Dependent

Abstract Aims Sodium-glucose-cotransporter-2 inhibitors showed favourable cardiovascular outcomes, but the underlying mechanisms are still elusive. This study investigated the mechanisms of empagliflozin in human and murine heart failure with preserved ejection fraction (HFpEF). Methods and results The acute mechanisms of empagliflozin were investigated in human myocardium from patients with HFpEF and murine ZDF obese rats, which were treated in vivo. As shown with immunoblots and ELISA, empagliflozin significantly suppressed increased levels of ICAM-1, VCAM-1, TNF-α, and IL-6 in human and murine HFpEF myocardium and attenuated pathological oxidative parameters (H2O2, 3-nitrotyrosine, GSH, lipid peroxide) in both cardiomyocyte cytosol and mitochondria in addition to improved endothelial vasorelaxation. In HFpEF, we found higher oxidative stress-dependent activation of eNOS leading to PKGIα oxidation. Interestingly, immunofluorescence imaging and electron microscopy revealed that oxidized PKG1α in HFpEF appeared as dimers/polymers localized to the outer-membrane of the cardiomyocyte. Empagliflozin reduced oxidative stress/eNOS-dependent PKGIα oxidation and polymerization resulting in a higher fraction of PKGIα monomers, which translocated back to the cytosol. Consequently, diminished NO levels, sGC activity, cGMP concentration, and PKGIα activity in HFpEF increased upon empagliflozin leading to improved phosphorylation of myofilament proteins. In skinned HFpEF cardiomyocytes, empagliflozin improved cardiomyocyte stiffness in an anti-oxidative/PKGIα-dependent manner. Monovariate linear regression analysis confirmed the correlation of oxidative stress and PKGIα polymerization with increased cardiomyocyte stiffness and diastolic dysfunction of the HFpEF patients. Conclusion Empagliflozin reduces inflammatory and oxidative stress in HFpEF and thereby improves the NO–sGC–cGMP–cascade and PKGIα activity via reduced PKGIα oxidation and polymerization leading to less pathological cardiomyocyte stiffness.

From comorbidities to heart failure with preserved ejection fraction: a story of oxidative stress

Heart ◽  
2015 ◽  
Vol 102 (4) ◽  
pp. 320-330 ◽  
Author(s):  
Constantijn Franssen ◽  
Sophia Chen ◽  
Nazha Hamdani ◽  
Walter J Paulus
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Preserved Ejection Fraction

scholarly journals The Oxidative Stress and Chronic Inflammatory Process in Chagas Disease: Role of Exosomes and Contributing Genetic Factors

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Edio Maldonado ◽  
Diego A. Rojas ◽  
Fabiola Urbina ◽  
Aldo Solari
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Heart Failure ◽  
Immune Response ◽  
Chronic Inflammation ◽  
Chagas Disease ◽  
Genetic Factors ◽  
Cardiac Tissue ◽  
Chronic Phase

Chagas disease is a neglected tropical disease caused by the flagellated protozoa Trypanosoma cruzi that affects several million people mainly in Latin American countries. Chagas disease has two phases, which are acute and chronic, both separated by an indeterminate time period in which the infected individual is relatively asymptomatic. The acute phase extends for 40-60 days with atypical and mild symptoms; however, about 30% of the infected patients will develop a symptomatic chronic phase, which is characterized by either cardiac, digestive, neurological, or endocrine problems. Cardiomyopathy is the most important and severe result of Chagas disease, which leads to left ventricular systolic dysfunction, heart failure, and sudden cardiac death. Most deaths are due to heart failure (70%) and sudden death (30%) resulting from cardiomyopathy. During the chronic phase, T. cruzi-infected macrophages respond with the production of proinflammatory cytokines and production of superoxide and nitric oxide by the NADPH oxidase 2 (NOX2) and inducible nitric oxide synthase (iNOS) enzymes, respectively. During the chronic phase, myocardial changes are produced as a result of chronic inflammation, oxidative stress, fibrosis, and cell death. The cellular inflammatory response is mainly the result of activation of the NF-κB-dependent pathway, which activates gene expression of inflammatory cytokines, leading to progressive tissue damage. The persisting production of reactive oxygen species (ROS) is the result of mitochondrial dysfunction in the cardiomyocytes. In this review, we will discuss inflammation and oxidative damage which is produced in the heart during the chronic phase of Chagas disease and recent evidence on the role of macrophages and the production of proinflammatory cytokines during the acute phase and the origin of macrophages/monocytes during the chronic phase of Chagas disease. We will also discuss the contributing factors and mechanisms leading to the chronic inflammation of the cardiac tissue during the chronic phase of the disease as well as the innate and adaptive host immune response. The contribution of genetic factors to the progression of the chronic inflammatory cardiomyopathy of chronic Chagas disease is also discussed. The secreted extracellular vesicles (exosomes) produced for both T. cruzi and infected host cells can play key roles in the host immune response, and those roles are described. Lastly, we describe potential treatments to attenuate the chronic inflammation of the cardiac tissue, designed to improve heart function in chagasic patients.

scholarly journals Increased nitrosative/oxidative stress lowers myocardial protein kinase G activity in heart failure with preserved ejection fraction

2013 ◽  
Vol 14 (S1) ◽  
Author(s):  
Loek van Heerebeek ◽  
Nazha Hamdani ◽  
Inês Falcão-Pires ◽  
Adelino F Leite-Moreira ◽  
Mark PV Begieneman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Protein Kinase ◽  
Ejection Fraction ◽  
Protein Kinase G ◽  
Preserved Ejection Fraction

scholarly journals OPLAH ablation leads to accumulation of 5-oxoproline, oxidative stress, fibrosis, and elevated fillings pressures: a murine model for heart failure with a preserved ejection fraction

2018 ◽  
Vol 114 (14) ◽  
pp. 1871-1882 ◽  
Author(s):  
Atze van der Pol ◽  
Andres Gil ◽  
Jasper Tromp ◽  
Herman H W Silljé ◽  
Dirk J van Veldhuisen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Murine Model ◽  
Preserved Ejection Fraction

Abstract 500: Basal Peripheral Arterial Blood Flow Increases Concomitantly with Decreased Cardiopulmonary Reserve and Biomarkers Activation in Patients with Heart Failure and Preserved Ejection Fraction

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Damien Vitiello ◽  
François Harel ◽  
Rhian M Touyz ◽  
Martin G Sirois ◽  
Joel Lavoie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Blood Flow ◽  
Arterial Blood Flow ◽  
Subclinical Inflammation ◽  
Preserved Ejection Fraction ◽  
Arterial Function ◽  
Arterial Blood ◽  
Peripheral Arterial ◽  
And Oxidative Stress

Background The underlying pathophysiology of heart failure with preserved ejection fraction (HFpEF) remains poorly understood. Changes in peripheral arterial function concomitantly with the evaluation of cardiopulmonary reserve and biomarkers related to wall stress, extra-cellular matrix turnover (ECM), subclinical inflammation and oxidative stress have not been investigated in patients with HFpEF nor compared with age-matched healthy volunteers (HV). We hypothesized that patients with HFpEF would have impairments in cardiac reserve with reduced peripheral arterial function associated with broad-spectrum biomarkers activation. Methods Eighteen male and female HFpEF patients (aged 70 ± 9 yr) NYHA class II and III were recruited. Data from patients were compared with those from 14 age and sex matched HV. A maximal exercise testing with gas exchange analysis was completed on a treadmill using a RAMP protocol and heart rate recovery (HRR) was measured at 1 and 2 minutes following exercise. Peripheral arterial function was assessed using near infrared radionuclide plethysmography. Biomarkers included BNP, NT-proBNP, hsCRP, TBARS, 8-epi-prostaglandin F2α, MMP 1, 2, 9 and TIMP 1, 2, 3, 4) were analyzed. Results Selected data are presented in the Table 1 and 2. Conclusions Compared to healthy volunteers, patients with HFpEF demonstrated a significant decrease in aerobic capacity but an increase in basal peripheral arterial blood flow, subclinical inflammation and oxidative stress. The increase in resting arterial blood flow may be a compensatory mechanism for the decrease in cardiac reserve and the pro-inflammatory/oxidant milieu in these patients.

scholarly journals Impact of acute antioxidant administration on inflammation and vascular function in heart failure with preserved ejection fraction

2019 ◽  
Vol 317 (5) ◽  
pp. R607-R614 ◽  
Author(s):  
Stephen M. Ratchford ◽  
Heather L. Clifton ◽  
Jayson R. Gifford ◽  
D. Taylor LaSalle ◽  
Taylor S. Thurston ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Vascular Function ◽  
Reactive Hyperemia ◽  
Protein Carbonyl ◽  
Microvascular Function ◽  
Preserved Ejection Fraction ◽  
Double Blind ◽  
No Bioavailability

Although it is now well established that heart failure with preserved ejection fraction (HFpEF) is associated with marked inflammation and a prooxidant state that is accompanied by vascular dysfunction, whether acute antioxidant (AO) administration can effectively target these disease-related decrements has not been evaluated. Thus, the present study sought to evaluate the efficacy of an acute over-the-counter AO cocktail (600 mg α-lipoic acid, 1,000 mg vitamin C, and 600 IU vitamin E) to mitigate inflammation and oxidative stress, and subsequently improve nitric oxide (NO) bioavailability and vascular function, in patients with HFpEF. Flow-mediated dilation (FMD) and reactive hyperemia (RH) were evaluated to assess conduit vessel and microvascular function, respectively, 90 min after administration of either placebo (PL) or AO in 16 patients with HFpEF (73 ± 10 yr, EF 54–70%) using a double-blind, crossover design. Circulating biomarkers of inflammation (C-reactive protein, CRP), oxidative stress (malondialdehyde and protein carbonyl), free radical concentration (EPR spectroscopy), antioxidant capacity, ascorbate and NO bioavailability (plasma nitrate, [Formula: see text], and nitrite, [Formula: see text]) were also assessed. FMD improved following AO administration (PL: 3.49 ± 0.7%, AO: 5.83 ± 1.0%), whereas RH responses were similar between conditions (PL: 428 ± 51 mL, AO: 425 ± 51 mL). AO administration decreased CRP (PL: 4,429 ± 705 ng/mL, AO: 3,664 ± 520 ng/mL) and increased ascorbate (PL: 30.0 ± 2.9 µg/mL, AO: 45.1 ± 3.7 µg/mL) and [Formula: see text] (PL: 182 ± 21 nM, AO: 213 ± 24 nM) but did not affect other biomarkers. Together, these data suggest that acute AO administration can exert anti-inflammatory effects and improve conduit artery vasodilation, but not microvascular function, in patients with HFpEF.

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