Role of inflammation, oxidative stress, and autonomic nervous system activation during the development of right and left cardiac remodeling in experimental pulmonary arterial hypertension

Zimmer, Alexsandra; Teixeira, Rayane Brinck; Bonetto, Jéssica Hellen Poletto; Bahr, Alan Christhian; Türck, Patrick; Castro, Alexandre Luz de; Carraro, Cristina Campos; Visioli, Fernanda; Fernandes-Piedras, Tânia Regina Gattelli; Casali, Karina Rabello; Scassola, Catharina M. Carvalho; Baldo, Guilherme; Araújo, Alex Sander da Rosa; Singal, Pawan K.; Belló‐Klein, Adriane

doi:10.1007/s11010-019-03652-2

Cited by 30 publications

(28 citation statements)

References 57 publications

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“…Recently, our group (Duchatsch et al, 2020) revealed that the same low‐dose of DEX used in this present study (50 μg/kg) decreased relative wall tension, increased internal diameters (LVDD and LVSD), increased LV vessel density and reduced myocardial collagen deposition, which most likely contributed to improve systolic and diastolic function in SHR, however, in that study systolic and diastolic function were reduced in SHR compared with Wistar rats before DEX treatment. Because myocardial remodeling may be somewhat determined by an inflammatory process (Cohn et al, 2000; Nian et al, 2004; Xie et al, 2019; Zimmer et al, 2020) and SHR presents higher levels of interleukin‐6 (IL‐6) and TNF‐α in the myocardium, accompanied by fibrotic infiltration and collagen deposition (Silva et al, 2017; Yao et al, 2009; You et al, 2018), it is possible to consider that DEX, which is a potent anti‐inflammatory drug, could decrease these inflammatory cytokines and improve cardiac fibrosis and collagen deposition (Xia et al, 2007) as shown in this present study. In agreement, in this present study, DEX treatment reduced the relative wall tension, increased the LV systolic diameter, and reduced the myocardial collagen deposition area; even though these responses were not sufficient to improve systolic function in SHR.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats

Tardelli

Duchatsch

Herrera

et al. 2021

J of Applied Toxicology

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Dexamethasone (DEX)‐induced hypertension is observed in normotensive rats, but little is known about the effects of DEX on spontaneously hypertensive animals (SHR). This study aimed to evaluate the effects of DEX on hemodynamics, cardiac hypertrophy and arterial stiffness in normotensive and hypertensive rats. Wistar rats and SHR were treated with DEX (50 μg/kg s.c., 14 d) or saline. Pulse wave velocity (PWV), echocardiographic parameters, blood pressure (BP), autonomic modulation and histological analyses of heart and thoracic aorta were performed. SHR had higher BP compared with Wistar, associated with autonomic unbalance to the heart. Echocardiographic changes in SHR (vs. Wistar) were suggestive of cardiac remodeling: higher relative wall thickness (RWT, +28%) and left ventricle mass index (LVMI, +26%) and lower left ventricle systolic diameter (LVSD, −19%) and LV diastolic diameter (LVDD, −10%), with slightly systolic dysfunction and preserved diastolic dysfunction. Also, SHR had lower myocardial capillary density and similar collagen deposition area. PWV was higher in SHR due to higher aortic collagen deposition. DEX‐treated Wistar rats presented higher BP (~23%) and autonomic unbalance. DEX did not change cardiac structure in Wistar, but PWV (+21%) and aortic collagen deposition area (+21%) were higher compared with control. On the other side, DEX did not change BP or autonomic balance to the heart in SHR, but reduced RWT and LV collagen deposition area (−12% vs. SHRCT). In conclusion, the results suggest a differential effect of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats.

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Section: Discussionmentioning

confidence: 99%

Differential effects of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats

Tardelli

Duchatsch

Herrera

et al. 2021

J of Applied Toxicology

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“…Based on these assumptions, the arrhythmia observed after carbofuran exposure might have been due to the damage in the central nervous system or pacemaker caused by ROS accumulation in the tissues [ 63 ]. Furthermore, like humans, the existence of pacemaker cells was also confirmed in zebrafish, wherein damage in these cells could impact the heart’s ability to maintain sinus rhythm [ 64 ]. Thus, we hypothesize that the cardiac damage come from the elevation of oxidative stress cause by copper oxide nanoparticle and the reduction of AChE activity caused by carbofuran ( Figure 10 ).…”

Section: Discussionmentioning

confidence: 99%

“…Molecular docking studies elucidated the binding mechanism of carbofuran as compared to ACh. The AChE active site is subdivided into the catalytic machinery and a choline-binding pocket, termed as the esteratic site and an anionic site, respectively [ 64 ]. The esteratic site contains a serine residue directly implicated in the hydrolysis of ACh, which in our case could be Ser225.…”

Section: Discussionmentioning

confidence: 99%

Co-Treatment of Copper Oxide Nanoparticle and Carbofuran Enhances Cardiotoxicity in Zebrafish Embryos

Saputra

Uapipatanakul

Lee

et al. 2021

IJMS

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The use of chemicals to boost food production increases as human consumption also increases. The insectidal, nematicidal and acaricidal chemical carbofuran (CAF), is among the highly toxic carbamate pesticide used today. Alongside, copper oxide nanoparticles (CuO) are also used as pesticides due to their broad-spectrum antimicrobial activity. The overuse of these pesticides may lead to leaching into the aquatic environments and could potentially cause adverse effects to aquatic animals. The aim of this study is to assess the effects of carbofuran and copper oxide nanoparticles into the cardiovascular system of zebrafish and unveil the mechanism behind them. We found that a combination of copper oxide nanoparticle and carbofuran increases cardiac edema in zebrafish larvae and disturbs cardiac rhythm of zebrafish. Furthermore, molecular docking data show that carbofuran inhibits acetylcholinesterase (AChE) activity in silico, thus leading to impair cardiac rhythms. Overall, our data suggest that copper oxide nanoparticle and carbofuran combinations work synergistically to enhance toxicity on the cardiovascular performance of zebrafish larvae.

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“…Lung slices were blindly analysed by an expert pathologist for the presence of macrophages, and inflammatory infiltrate qualitatively defined as absent (0) or present. If present, it was classified as mild (1), moderate (2) or accentuated (3), according to the number of inflammatory cells and extension of the infiltrate, as previous described (Zimmer et al., 2020). Images were obtained by a microscope‐coupled camera, model LOPT14003 (Opticam Microscopy Technology, São Paulo, SP, Brazil).…”

Section: Methodsmentioning

confidence: 99%

Thyroid hormone treatment improved the response to maximum exercise test and preserved the ventricular geometry in myocardial infarcted rats

Teixeira

Zimmer

Godoy

et al. 2020

Experimental Physiology

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New Findings What is the central question of this study?Does thyroid hormone treatment given after myocardial infarction preserve left ventricular function and treadmill exercise performance, and improve parameters of oxidative stress in the right ventricle and lungs of Wistar rats? What is the main finding and its importance?Thyroid hormone treatment improved the performance of the maximum exercise test in infarcted rats and induced effects in the heart and lungs that were similar to those observed with exercise training. This suggests there is a significant value of thyroid hormones for preserving exercise tolerance after myocardial infarction. Abstract Left ventricular myocardial infarction (MI) provokes damage in the heart and in other tissues, such as right ventricle and lungs. The present study elucidated whether thyroid hormone treatment (THT) may present positive effects in heart and lungs after MI, and whether or not these effects are similar to those of exercise training (ET). Male Wistar rats were divided into four groups: sham operated (SHAM), infarcted (MI), infarcted + exercise training (MIE), and infarcted + thyroid hormones (MIH). A maximum exercise test, left ventricle echocardiography, pulmonary histology, and oxidative stress in the right ventricle and lung were evaluated. THT and ET both reduced left ventricular dilatation and end‐diastolic wall stress indexes to a similar extent. MI accentuated the content of macrophages and inflammatory infiltrate in the lungs, which was partially prevented in the MIH and MIE groups. THT and ET presented similar effects in the heart and lungs, and both improved the performance of the maximum exercise test in infarcted animals.

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Role of inflammation, oxidative stress, and autonomic nervous system activation during the development of right and left cardiac remodeling in experimental pulmonary arterial hypertension

Cited by 30 publications

References 57 publications

Differential effects of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats

Differential effects of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats

Co-Treatment of Copper Oxide Nanoparticle and Carbofuran Enhances Cardiotoxicity in Zebrafish Embryos

Thyroid hormone treatment improved the response to maximum exercise test and preserved the ventricular geometry in myocardial infarcted rats

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