Hyper-Inflammatory Response Involves in Cardiac Injury among Patients with Coronavirus Disease 2019

Background. Numerous studies have demonstrated that the inflammatory response is involved in the progression of lipopolysaccharide- (LPS-) induced myocardial cell apoptosis. Accumulating evidence has shown that thyroxine participates in diseases by downregulating the inflammatory response. This study aimed at investigating whether thyroxine alleviates LPS-induced myocardial cell apoptosis. Methods. Bone marrow-derived macrophages (Mø) were treated with LPS and thyroxine, and Mø differentiation and Mø-related cytokine expression were measured. The effect of Mø differentiation on mouse cardiomyocyte (MCM) apoptosis was also detected in vitro. In addition, C57BL/6 mice underwent thyroidectomy and were treated with LPS 35 days later; subsequently, Mø differentiation and myocardial cell apoptosis in hearts were analyzed. To determine whether the nuclear factor-kappa B (NF-κB) p65 pathway mediates the effect of thyroxine on Mø differentiation and myocardial cell apoptosis, the specific NF-κB p65 pathway inhibitor JSH-23 was administered to mice that underwent a thyroidectomy. Results. Levothyroxine treatment significantly reduced the activation of the NF-κB p65 pathway, decreased M1 macrophage (Mø1) differentiation and Mø1-related cytokine mRNA levels in LPS-treated Mø, and increased M2 macrophage (Mø2) differentiation and Mø2-related cytokine mRNA expression. The protective effects of levothyroxine on MCM apoptosis mediated by LPS-treated Mø were alleviated by JSH-23. In mice, thyroidectomy aggravated LPS-induced cardiac injury and cardiac dysfunction, further promoted NF-κB p65 activation, and increased cardiac Mø1 expression and myocardial cell apoptosis but decreased cardiac Mø2 expression. JSH-23 treatment significantly ameliorated the thyroidectomy-induced increases in myocardial cell apoptosis and Mø differentiation. Conclusions. Thyroxine alleviated the Mø1/Mø2 imbalance, reduced the inflammatory response, decreased myocardial cell apoptosis, and protected against cardiac injury and cardiac dysfunction in LPS-treated mice. Thyroxine may be a novel therapeutic strategy to prevent and treat LPS-induced cardiac injury.

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Interleukin-27 attenuates myocardial injury after ischemia-reperfusion through down-regulation of inflammatory response

American Journal of BioMedicine ◽

10.18081/2333-5106/019-02/104-117 ◽

2021 ◽

Vol 9 (1) ◽

pp. 62-75

Author(s):

Mai HN ◽

Lee YS

Keyword(s):

Inflammatory Response ◽

Ventricular Function ◽

Myocardial Injury ◽

Myocardial Dysfunction ◽

Ischemia Reperfusion ◽

Cardiac Injury ◽

Left Ventricular ◽

Mice Model ◽

Down Regulation ◽

Stat Pathway

The proinflammatory cytokines may mediate myocardial dysfunction associated with myocardial injury and inflammatory response is an important process during the pathogenesis of myocardial I/R injury. IL-27, this cytokine is mainly produced by cells of myeloid origin such as monocytes, macrophages, dendritic cells, and microglial cells, in response to stimuli acting through Toll-like receptors. The objective of present study is to assess whether IL-27 can improve ventricular function after myocardial ischemia by down-regulation of inflammatory response. The results demonstrated that the IL-27 markedly attenuated Left Ventricular Function (LVF) in mice model, and reduced plasma level of cTn-I as marker of cardiac injury. Moreover, the IL-27 was associated with up-regulation in both chemokine and cytokines expression following I/R, through down-regulation of activation of JAK/STAT pathway.

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Specific macrophage populations promote both cardiac scar deposition and subsequent resolution in adult zebrafish

Cardiovascular Research ◽

10.1093/cvr/cvz221 ◽

2019 ◽

Vol 116 (7) ◽

pp. 1357-1371 ◽

Cited By ~ 10

Author(s):

Laura Bevan ◽

Zhi Wei Lim ◽

Byrappa Venkatesh ◽

Paul R Riley ◽

Paul Martin ◽

...

Keyword(s):

Inflammatory Response ◽

Inflammatory Cell ◽

Inflammatory Responses ◽

Tissue Injury ◽

Cardiac Injury ◽

Repair Process ◽

Adult Zebrafish ◽

Cardiac Damage ◽

Scar Resolution ◽

Macrophage Subsets

Abstract Aims A robust inflammatory response to tissue injury is a necessary part of the repair process but the deposition of scar tissue is a direct downstream consequence of this response in many tissues including the heart. Adult zebrafish not only possess the capacity to regenerate lost cardiomyocytes but also to remodel and resolve an extracellular scar within tissues such as the heart, but this scar resolution process remains poorly understood. This study aims to characterize the scarring and inflammatory responses to cardiac damage in adult zebrafish in full and investigate the role of different inflammatory subsets specifically in scarring and scar removal. Methods and results Using stable transgenic lines, whole organ imaging and genetic and pharmacological interventions, we demonstrate that multiple inflammatory cell lineages respond to cardiac injury in adult zebrafish. In particular, macrophage subsets (tnfα+ and tnfα−) play prominent roles with manipulation of different phenotypes suggesting that pro-inflammatory (tnfα+) macrophages promote scar deposition following cardiac injury whereas tnfα− macrophages facilitate scar removal during regeneration. Detailed analysis of these specific macrophage subsets reveals crucial roles for Csf1ra in promoting pro-inflammatory macrophage-mediated scar deposition. Additionally, the multifunctional cytokine Osteopontin (Opn) (spp1) is important for initial scar deposition but also for resolution of the inflammatory response and in late-stage ventricular collagen remodelling. Conclusions This study demonstrates the importance of a correctly balanced inflammatory response to facilitate scar deposition during repair but also to allow subsequent scar resolution, and full cardiac regeneration, to occur. We have identified Opn as having both pro-fibrotic but also potentially pro-regenerative roles in the adult zebrafish heart, driving Collagen deposition but also controlling inflammatory cell resolution.

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Rosuvastatin corrects oxidative stress and inflammation induced by LPS to attenuate cardiac injury by inhibiting the NLRP3/TLR4 pathway

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2020-0321 ◽

2021 ◽

Author(s):

Guocheng Ren ◽

Qiujie Zhou ◽

Meili Lu ◽

Hongxin Wang

Keyword(s):

Oxidative Stress ◽

Inflammatory Response ◽

Cardiac Injury ◽

H9c2 Cells ◽

Sod Activity ◽

Lps Challenge ◽

Pathway Activation ◽

Underlying Mechanisms

The aim of the current study was to evaluate whether rosuvastatin was effective in attenuating cardiac injury in lipopolysaccharide(LPS)-challenged mice and H9C2 cells and identify the underlying mechanisms, focusing on the NLRP3/TLR4 pathway. Cardiac injury, cardiac function, apoptosis, oxidative stress, inflammatory response and the NLRP3/TLR4 pathway were evaluated in both in vivo and in vitro studies. LPS-induced cardiomyocytes injury was markedly attenuated by rosuvastatin treatment. Apoptosis was clearly ameliorated in myocardial tissue and H9C2 cells cotreated with rosuvastatin. In addition, excessive oxidative stress was present, as indicated by increases in MDA content, NADPH activity and ROS production and decreased SOD activity after LPS challenge. Rosuvastatin improved all the indicators of oxidative stress, with a similar effect to NAC(ROS scavenger). Notably, LPS-exposed H9C2 cells and mice showed significant NLRP3 and TLR4/NF-κB pathway activation. Administration of rosuvastatin reduced the increases in expression of NLRP3, ASC, pro-caspase-1, TLR4, and p65 and decreased the contents of TNF-α, IL-1β, IL-18 and IL-6, with a similar effect as MCC950 (NLRP3 inhibitor). In conclusion, inhibition of the inflammatory response and oxidative stress contributes to cardioprotection of rosuvastatin on cardiac injury induced by LPS, and the effect of rosuvastatin was achieved by inactivation of the NF-κB/NLRP3 pathway

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Vitamin E and telmisartan attenuates doxorubicin induced cardiac injury in rat through down regulation of inflammatory response

BMC Cardiovascular Disorders ◽

10.1186/1471-2261-12-63 ◽

2012 ◽

Vol 12 (1) ◽

Cited By ~ 38

Author(s):

Najah Hadi ◽

Nasser Ghaly Yousif ◽

Fadhil G Al-amran ◽

Nadhem K Huntei ◽

Bassim I Mohammad ◽

...

Keyword(s):

Vitamin E ◽

Inflammatory Response ◽

Cardiac Injury ◽

Down Regulation

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The microRNA-221/-222 cluster balances the antiviral and inflammatory response in viral myocarditis

European Heart Journal ◽

10.1093/eurheartj/ehv321 ◽

2015 ◽

Vol 36 (42) ◽

pp. 2909-2919 ◽

Cited By ~ 49

Author(s):

Maarten F Corsten ◽

Ward Heggermont ◽

Anna-Pia Papageorgiou ◽

Sophie Deckx ◽

Aloys Tijsma ◽

...

Keyword(s):

Viral Load ◽

Inflammatory Response ◽

Viral Replication ◽

Cardiac Injury ◽

Viral Myocarditis ◽

Inflammatory Cells ◽

Cardiac Cells ◽

Cardiac Response ◽

Cvb3 Infection

Abstract Aims Viral myocarditis (VM) is an important cause of heart failure and sudden cardiac death in young healthy adults; it is also an aetiological precursor of dilated cardiomyopathy. We explored the role of the miR-221/-222 family that is up-regulated in VM. Methods and results Here, we show that microRNA-221 (miR-221) and miR-222 levels are significantly elevated during acute VM caused by Coxsackievirus B3 (CVB3). Both miRs are expressed by different cardiac cells and by infiltrating inflammatory cells, but their up-regulation upon myocarditis is mostly exclusive for the cardiomyocyte. Systemic inhibition of miR-221/-222 in mice increased cardiac viral load, prolonged the viraemic state, and strongly aggravated cardiac injury and inflammation. Similarly, in vitro, overexpression of miR-221 and miR-222 inhibited enteroviral replication, whereas knockdown of this miR-cluster augmented viral replication. We identified and confirmed a number of miR-221/-222 targets that co-orchestrate the increased viral replication and inflammation, including ETS1/2, IRF2, BCL2L11, TOX, BMF, and CXCL12. In vitro inhibition of IRF2, TOX, or CXCL12 in cardiomyocytes significantly dampened their inflammatory response to CVB3 infection, confirming the functionality of these targets in VM and highlighting the importance of miR-221/-222 as regulators of the cardiac response to VM. Conclusions The miR-221/-222 cluster orchestrates the antiviral and inflammatory immune response to viral infection of the heart. Its inhibition increases viral load, inflammation, and overall cardiac injury upon VM.

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High-doses vitamin C improves cardiac injury through preventing hyper-inflammatory response in coronavirus disease 2019

10.22541/au.159645451.16478965 ◽

2020 ◽

Author(s):

Guozhi Xia ◽

Di Fan ◽

Chaoran Ma ◽

Yanru He ◽

Ming Wang ◽

...

Keyword(s):

Vitamin C ◽

Inflammatory Response ◽

Cardiac Injury ◽

High Doses

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Doxorubicin-Induced Cardiac Abnormalities in Rats: Attenuation via Sandalwood Oil

Pharmacology ◽

10.1159/000504372 ◽

2019 ◽

Vol 105 (9-10) ◽

pp. 522-530 ◽

Cited By ~ 1

Author(s):

Nancy S. Younis

Keyword(s):

Inflammatory Response ◽

Troponin T ◽

Cardiac Injury ◽

Cardiac Biomarkers ◽

Sprague Dawley ◽

Necrosis Factor Alpha ◽

Group 4 ◽

Sprague Dawley Rats ◽

Sandalwood Oil ◽

Group 2

Introduction: The clinical use of doxorubicin (DOX) is challenged by its incremental dose-related cardiotoxicity. Objective: The aim of the hereby study was to investigate sandalwood essential oil (SEO) against DOX-induced cardiac toxicity. Methods: Male Sprague-Dawley rats were allocated into 4 groups. Groups 1 signified the control, whereas group 2 administered 100 mg/kg/day SEO, both act as control. In group 3, DOX was given intraperitoneal in a dose of 3 mg/kg/ every other day for 2 weeks to induced cardiotoxicity. While group 4 received a combination of SEO and DOX for 2 weeks. DOX prompted variations were assessed by measuring cardiac injury biomarkers, including creatine phosphokinase, cardiac troponin T, and lactate dehydrogenase (LDH), electrocardiogram (ECG) fluctuations, heart rate (HR), and blood pressure (BP) indices. The effect of both DOX and SEO on various antioxidants such as glutathione, superoxide dismutase, and catalase and inflammatory mediators including interleukin-1β, tumor necrosis factor-alpha, and NF-κB was quantified. Results: DOX augmented cardiac injury biomarkers, altered ECG, deceased HR and antioxidants, and finally increased BP indices. Treatment with SEO significantly (p < 0.05) decreased cardiac biomarkers and reversing ECG changes and BP. Moreover, treatment with SEO enhanced HR anomalies and antioxidant activity reduction and precluded the intensive inflammatory response induced by DOX. Conclusion: SEO may have the potential of mitigating cardiac rhythm and BP indices changes induced with DOX. SEO modifications may be due to antioxidant capacity improvement and inflammatory response prohibition of the heart muscle.

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Cortical bone stem cells modify cardiac inflammation after myocardial infarction by inducing a novel macrophage phenotype

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00304.2021 ◽

2021 ◽

Vol 321 (4) ◽

pp. H684-H701

Author(s):

Alexander R. H. Hobby ◽

Remus M. Berretta ◽

Deborah M. Eaton ◽

Hajime Kubo ◽

Eric Feldsott ◽

...

Keyword(s):

Myocardial Infarction ◽

Stem Cells ◽

Stem Cell ◽

Inflammatory Response ◽

Cell Therapy ◽

Cortical Bone ◽

Cardiac Injury ◽

Macrophage Phenotype ◽

Cardiac Inflammation

Cortical bone stem cell (CBSC) therapy after myocardial infarction alters the inflammatory response to cardiac injury. We found that cortical bone stem cell therapy induces a unique macrophage phenotype in vitro and can modulate macrophage/fibroblast cross talk.

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