scholarly journals Stimulating pro-reparative immune responses to prevent adverse cardiac remodelling: consensus document from the joint 2019 meeting of the ESC Working Groups of cellular biology of the heart and myocardial function

2020 ◽  
Vol 116 (11) ◽  
pp. 1850-1862 ◽  
Author(s):  
Sabine Steffens ◽  
Sophie Van Linthout ◽  
Joost P G Sluijter ◽  
Carlo Gabriele Tocchetti ◽  
Thomas Thum ◽  
...  
Keyword(s):  
Immune Cells ◽  
Tissue Damage ◽  
Cardiac Tissue ◽  
Cardiac Injury ◽  
Experimental Studies ◽  
Cardiac Remodelling ◽  
Cardiac Inflammation ◽  
Consensus Document ◽  
Working Groups ◽  
Underlying Pathophysiology

Abstract Cardiac injury may have multiple causes, including ischaemic, non-ischaemic, autoimmune, and infectious triggers. Independent of the underlying pathophysiology, cardiac tissue damage induces an inflammatory response to initiate repair processes. Immune cells are recruited to the heart to remove dead cardiomyocytes, which is essential for cardiac healing. Insufficient clearance of dying cardiomyocytes after myocardial infarction (MI) has been shown to promote unfavourable cardiac remodelling, which may result in heart failure (HF). Although immune cells are integral key players of cardiac healing, an unbalanced or unresolved immune reaction aggravates tissue damage that triggers maladaptive remodelling and HF. Neutrophils and macrophages are involved in both, inflammatory as well as reparative processes. Stimulating the resolution of cardiac inflammation seems to be an attractive therapeutic strategy to prevent adverse remodelling. Along with numerous experimental studies, the promising outcomes from recent clinical trials testing canakinumab or colchicine in patients with MI are boosting the interest in novel therapies targeting inflammation in cardiovascular disease patients. The aim of this review is to discuss recent experimental studies that provide new insights into the signalling pathways and local regulators within the cardiac microenvironment promoting the resolution of inflammation and tissue regeneration. We will cover ischaemia- and non-ischaemic-induced as well as infection-related cardiac remodelling and address potential targets to prevent adverse cardiac remodelling.

scholarly journals Emerging Roles for Immune Cells and MicroRNAs in Modulating the Response to Cardiac Injury

2019 ◽  
Vol 6 (1) ◽  
pp. 5 ◽  
Author(s):  
Adriana Rodriguez ◽  
Viravuth Yin
Keyword(s):  
Immune Cells ◽  
Cardiac Tissue ◽  
Heart Function ◽  
Cardiac Injury ◽  
Scar Tissue ◽  
Acute Injury ◽  
Heart Regeneration ◽  
Cardiomyocyte Proliferation ◽  
Cardiac Damage ◽  
Dynamic Interplay

Stimulating cardiomyocyte regeneration after an acute injury remains the central goal in cardiovascular regenerative biology. While adult mammals respond to cardiac damage with deposition of rigid scar tissue, adult zebrafish and salamander unleash a regenerative program that culminates in new cardiomyocyte formation, resolution of scar tissue, and recovery of heart function. Recent studies have shown that immune cells are key to regulating pro-inflammatory and pro-regenerative signals that shift the injury microenvironment toward regeneration. Defining the genetic regulators that control the dynamic interplay between immune cells and injured cardiac tissue is crucial to decoding the endogenous mechanism of heart regeneration. In this review, we discuss our current understanding of the extent that macrophage and regulatory T cells influence cardiomyocyte proliferation and how microRNAs (miRNAs) regulate their activity in the injured heart.

scholarly journals Role of Cardiac Macrophages on Cardiac Inflammation, Fibrosis and Tissue Repair

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 51
Author(s):  
William P. Lafuse ◽  
Daniel J. Wozniak ◽  
Murugesan V. S. Rajaram
Keyword(s):  
Tissue Damage ◽  
Tissue Repair ◽  
Cardiac Tissue ◽  
Tissue Injury ◽  
The Body ◽  
T And B Cells ◽  
Functional Changes ◽  
Cardiac Inflammation ◽  
And Function

The immune system plays a pivotal role in the initiation, development and resolution of inflammation following insult or damage to organs. The heart is a vital organ which supplies nutrients and oxygen to all parts of the body. Heart failure (HF) has been conventionally described as a disease associated with cardiac tissue damage caused by systemic inflammation, arrhythmia and conduction defects. Cardiac inflammation and subsequent tissue damage is orchestrated by the infiltration and activation of various immune cells including neutrophils, monocytes, macrophages, eosinophils, mast cells, natural killer cells, and T and B cells into the myocardium. After tissue injury, monocytes and tissue-resident macrophages undergo marked phenotypic and functional changes, and function as key regulators of tissue repair, regeneration and fibrosis. Disturbance in resident macrophage functions such as uncontrolled production of inflammatory cytokines, growth factors and inefficient generation of an anti-inflammatory response or unsuccessful communication between macrophages and epithelial and endothelial cells and fibroblasts can lead to aberrant repair, persistent injury, and HF. Therefore, in this review, we discuss the role of cardiac macrophages on cardiac inflammation, tissue repair, regeneration and fibrosis.

scholarly journals A double-edged sword of immuno-microenvironment in cardiac homeostasis and injury repair

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kang Sun ◽  
Yi-yuan Li ◽  
Jin Jin
Keyword(s):  
Nk Cells ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Early Stage ◽  
Cardiac Injury ◽  
Inflammatory Cells ◽  
Treg Cells ◽  
Scar Formation

AbstractThe response of immune cells in cardiac injury is divided into three continuous phases: inflammation, proliferation and maturation. The kinetics of the inflammatory and proliferation phases directly influence the tissue repair. In cardiac homeostasis, cardiac tissue resident macrophages (cTMs) phagocytose bacteria and apoptotic cells. Meanwhile, NK cells prevent the maturation and transport of inflammatory cells. After cardiac injury, cTMs phagocytose the dead cardiomyocytes (CMs), regulate the proliferation and angiogenesis of cardiac progenitor cells. NK cells prevent the cardiac fibrosis, and promote vascularization and angiogenesis. Type 1 macrophages trigger the cardioprotective responses and promote tissue fibrosis in the early stage. Reversely, type 2 macrophages promote cardiac remodeling and angiogenesis in the late stage. Circulating macrophages and neutrophils firstly lead to chronic inflammation by secreting proinflammatory cytokines, and then release anti-inflammatory cytokines and growth factors, which regulate cardiac remodeling. In this process, dendritic cells (DCs) mediate the regulation of monocyte and macrophage recruitment. Recruited eosinophils and Mast cells (MCs) release some mediators which contribute to coronary vasoconstriction, leukocyte recruitment, formation of new blood vessels, scar formation. In adaptive immunity, effector T cells, especially Th17 cells, lead to the pathogenesis of cardiac fibrosis, including the distal fibrosis and scar formation. CMs protectors, Treg cells, inhibit reduce the inflammatory response, then directly trigger the regeneration of local progenitor cell via IL-10. B cells reduce myocardial injury by preserving cardiac function during the resolution of inflammation.

scholarly journals Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

2021 ◽  
Vol 22 (6) ◽  
pp. 2902
Author(s):  
Ignacio Hernandez ◽  
Laura Tesoro ◽  
Rafael Ramirez-Carracedo ◽  
Javier Diez-Mata ◽  
Sandra Sanchez ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Cyclophilin A ◽  
Cardiac Ischemia ◽  
Cardiac Protection ◽  
Cardiac Inflammation ◽  
Risk Areas ◽  
Lysosome Degradation ◽  
Cardiac Necrosis

In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0.3 mg/kg Ivabradine significantly improved cardiac function and reduced cardiac necrosis by day 7 after IR, detecting a significant increase in cardiac CyPA in the necrotic compared to the risk areas, which was inversely correlated with the levels of circulating CyPA detected in plasma samples from the same subjects. In testing whether Ivabradine may regulate the levels of CyPA, no changes in tissue CyPA were found in healthy pigs treated with 0.3 mg/kg Ivabradine, but interestingly, when analyzing the complex EMMPRIN/CyPA, rather high glycosylated EMMPRIN, which is required for EMMPRIN-mediated matrix metalloproteinase (MMP) activation and increased CyPA bonding to low-glycosylated forms of EMMPRIN were detected by day 7 after IR in pigs treated with Ivabradine. To study the mechanism by which Ivabradine may prevent secretion of CyPA, we first found that Ivabradine was time-dependent in inhibiting co-localization of CyPA with the granule exocytosis marker vesicle-associated membrane protein 1 (VAMP1). However, Ivabradine had no effect on mRNA expression nor in the proteasome and lysosome degradation of CyPA. In conclusion, our results point toward CyPA, its ligand EMMPRIN, and the complex CyPA/EMMPRIN as important targets of Ivabradine in cardiac protection against IR.

Involvement of monocytes/macrophages as key factors in the development and progression of cardiovascular diseases

2014 ◽  
Vol 458 (2) ◽  
pp. 187-193 ◽  
Author(s):  
María Fernández-Velasco ◽  
Silvia González-Ramos ◽  
Lisardo Boscá
Keyword(s):  
Myocardial Infarction ◽  
Immune System ◽  
Cardiovascular Diseases ◽  
Cardiac Tissue ◽  
Initial Period ◽  
Cardiac Injury ◽  
Key Factors ◽  
Cardiac Damage ◽  
Inflammatory Profile

Emerging evidence points to the involvement of specialized cells of the immune system as key drivers in the pathophysiology of cardiovascular diseases. Monocytes are an essential cell component of the innate immune system that rapidly mobilize from the bone marrow to wounded tissues where they differentiate into macrophages or dendritic cells and trigger an immune response. In the healthy heart a limited, but near-constant, number of resident macrophages have been detected; however, this number significantly increases during cardiac damage. Shortly after initial cardiac injury, e.g. myocardial infarction, a large number of macrophages harbouring a pro-inflammatory profile (M1) are rapidly recruited to the cardiac tissue, where they contribute to cardiac remodelling. After this initial period, resolution takes place in the wound, and the infiltrated macrophages display a predominant deactivation/pro-resolution profile (M2), promoting cardiac repair by mediating pro-fibrotic responses. In the present review we focus on the role of the immune cells, particularly in the monocyte/macrophage population, in the progression of the major cardiac pathologies myocardial infarction and atherosclerosis.

Omentin-1 attenuates glucocorticoid-induced cardiac injury by phosphorylating GSK3β

2021 ◽  
Vol 66 (4) ◽  
pp. 273-283
Author(s):  
Zhousheng Jin ◽  
Fangfang Xia ◽  
Jiaojiao Dong ◽  
Tingting Lin ◽  
Yaoyao Cai ◽  
...  
Keyword(s):  
Side Effects ◽  
Cardiac Hypertrophy ◽  
Cardiac Injury ◽  
Experimental Studies ◽  
Chronic Administration ◽  
Cardiovascular Complications ◽  
Rat Serum ◽  
Cardiac Side Effects ◽  
Beneficial Effects

Glucocorticoid excess often causes a variety of cardiovascular complications, including hypertension, atherosclerosis, and cardiac hypertrophy. To abrogate its cardiac side effects, it is necessary to fully disclose the pathophysiological role of glucocorticoid in cardiac remodelling. Previous clinical and experimental studies have found that omentin-1, one of the adipokines, has beneficial effects in cardiovascular diseases, and is closely associated with metabolic disorders. However, there is no evidence to address the potential role of omentin-1 in glucocorticoid excess-induced cardiac injuries. To uncover the links, the present study utilized rat model with glucocorticoid-induced cardiac injuries and clinical patients with abnormal cardiac function. Chronic administration of glucocorticoid excess reduced rat serum omentin-1 concentration, which closely correlated with cardiac functional parameters. Intravenous administration of adeno-associated virus encoding omentin-1 upregulated the circulating omentin-1 level and attenuated glucocorticoid excess-induced cardiac hypertrophy and functional disorders. Overexpression of omentin-1 also improved cardiac mitochondrial function, including the reduction of lipid deposits, induction of mitochondrial biogenesis, and enhanced mitochondrial activities. Mechanistically, omentin-1 phosphorylated and activated the GSK3β pathway in the heart. From a study of 28 patients with Cushing’s syndrome and 23 healthy subjects, the plasma level of glucocorticoid was negatively correlated with omentin-1, and was positively associated with cardiac ejection fraction and fractional shortening. Collectively, the present study provided a novel role of omentin-1 in glucocorticoid excess-induced cardiac injuries and found that the omentin-1/GSK3β pathway was a potential therapeutic target in combating the side effects of glucocorticoid.

scholarly journals Whole Transcriptome Analysis of Hypertension Induced Cardiac Injury Using Deep Sequencing

2016 ◽  
Vol 38 (2) ◽  
pp. 670-682 ◽  
Author(s):  
Tao-Tao Li ◽  
Xiao-Yan Li ◽  
Li-Xin Jia ◽  
Jing Zhang ◽  
Wen-Mei Zhang ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Cell Activation ◽  
Critical Role ◽  
Cardiac Injury ◽  
Interaction Network ◽  
Receptor Interaction ◽  
Rna Seq ◽  
Cardiac Inflammation ◽  
Molecular Events ◽  
Focal Adhesion Protein

Background/Aims: Hypertension plays a critical role in the cardiac inflammation and injury. However, the mechanism of how hypertension causes the cardiac injury at a molecular level remains to be elucidated. Methods: RNA-Seq has been demonstrated to be an effective approach for transcriptome analysis, which is essential to reveal the molecular constituents of cells and tissues. In this study, we investigated the global molecular events associated with the mechanism of hypertension induced cardiac injury using RNA-Seq analysis. Results: Our results showed that totally 1,801 genes with different expression variations were identified after Ang II infusion at 1, 3 and 7 days. Go analysis showed that the top 5 high enrichment Go terms were response to stress, response to wounding, cellular component organization, cell activation and defense response. KEGG pathway analysis revealed the top 5 significantly overrepresented pathways were associated with ECM-receptor interaction, focal adhesion, protein digestion and absorption, phagosome and asthma. Moreover, protein-protein interaction network analysis indicated that ubiquitin C may play a key role in the processes of hypertension-induced cardiac injury. Conclusion: Our study provides a comprehensive understanding of the transcriptome events in hypertension-induced cardiac pathology.

scholarly journals Optogenetic currents in myofibroblasts acutely alter electrophysiology and conduction of co-cultured cardiomyocytes

2020 ◽  
Author(s):  
Geran Kostecki ◽  
Yu Shi ◽  
Christopher Chen ◽  
Daniel H. Reich ◽  
Emilia Entcheva ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Cardiac Injury ◽  
Neonatal Rat ◽  
Culture Studies ◽  
Electrophysiological Properties ◽  
Inward Currents ◽  
Life Threatening ◽  
Cultured Cardiomyocytes ◽  
Cardiac Myofibroblasts

AbstractInteractions between cardiac myofibroblasts and myocytes may slow conduction after cardiac injury, increasing the chance of life-threatening arrhythmia. While co-culture studies have shown that myofibroblasts can affect cardiomyocyte electrophysiology in vitro, the mechanism(s) remain debatable. In this study, primary neonatal rat cardiac myofibroblasts were transduced with the light-activated ion channel Channelrhodopsin-2, which allowed acute and selective modulation of myofibroblast currents in co-cultures with cardiomyocytes. Optical mapping revealed that myofibroblast-specific optogenetically induced inward currents decreased conduction velocity in the co-cultures by 27±6% (baseline = 17.7±5.3 cm/s), and shortened the cardiac action potential duration by 14±7% (baseline = 161±11 ms) when 0.017 mW/mm2 light was applied. When light irradiance was increased to 0.057 mW/mm2, the myofibroblast currents led to spontaneous beating in 6/7 co-cultures. Experiments showed that optogenetic perturbation did not lead to changes in myofibroblast strain and force generation, suggesting purely electrical effects in this model. In silico modeling of optogenetically modified myofibroblast-cardiomyocyte co-cultures largely reproduced these results and enabled a comprehensive study of relevant parameters. These results clearly demonstrate that myofibroblasts are sufficiently electrically connected to cardiomyocytes to effectively alter macroscopic electrophysiological properties in this model of cardiac tissue.

scholarly journals Chemokine receptor trafficking coordinates neutrophil clustering and dispersal at wounds in zebrafish

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Caroline Coombs ◽  
Antonios Georgantzoglou ◽  
Hazel A. Walker ◽  
Julian Patt ◽  
Nicole Merten ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Chemokine Receptor ◽  
Immune Cells ◽  
Tissue Damage ◽  
Chemokine Receptors ◽  
Inflammatory Responses ◽  
Receptor Trafficking ◽  
Migratory Response ◽  
Cell Behaviors ◽  
Downstream Signaling

AbstractImmune cells congregate at specific loci to fight infections during inflammatory responses, a process that must be transient and self-resolving. Cell dispersal promotes resolution, but it remains unclear how transition from clustering to dispersal is regulated. Here we show, using quantitative live imaging in zebrafish, that differential ligand-induced trafficking of chemokine receptors such as Cxcr1 and Cxcr2 orchestrates the state of neutrophil congregation at sites of tissue damage. Through receptor mutagenesis and biosensors, we show that Cxcr1 promotes clustering at wound sites, but is promptly desensitized and internalized, which prevents excess congregation. By contrast, Cxcr2 promotes bidirectional motility and is sustained at the plasma membrane. Persistent plasma membrane residence of Cxcr2 prolongs downstream signaling and is required for sustained exploratory motion conducive to dispersal. Thus, differential trafficking of two chemokine receptors allows coordination of antagonistic cell behaviors, promoting a self-resolving migratory response.

scholarly journals PENINGKATAN HIGH-SENSITIVE CARDIAC TROPONIN (HS-CTN) SETELAH LATIHAN INTENSITAS TINGGI YANG INTENSIF

2019 ◽  
Author(s):  
Indira Vidiari J ◽  
Nila Wahyuni ◽  
I Putu Adiartha Griadhi
Keyword(s):  
High Intensity ◽  
Cardiac Troponin ◽  
Meta Analysis ◽  
Cardiac Injury ◽  
High Sensitivity ◽  
Cardiac Damage ◽  
Intensive Exercise ◽  
Different Types ◽  
Underlying Pathophysiology

ABSTRACTThe role of exercise as a strategy for prevention, management and therapy in cardiovascular disease has been well described, but in some studies, it has been suggested that there is an increase in biomarkers in cardiac damage or cardiac troponin (cTn) after intensive, high-intensity exercise in healthy individuals. Several studies have shown significant increases in cardiac troponins after different types of exercise. The latest meta-analysis, showing that high-sensitivity cardiac troponin (hs-cTn) increases in about 83% of individuals after long and intensive exercise. The current pathophysiology of hs-cTn is not well understood. Several hypotheses have been proposed, such as transmembrane leakage from cytoplasmic free cTnT and cTnI or decreased troponin clearance from plasma, both caused by overloading of free radicals, myocardial stretching, elevated core temperature, or alteration of pH. Further research is needed with a full prospective study to evaluate the underlying pathophysiology of enhancing high sentivity cardiac troponin (hs-cTn) is an effective strategy for preventing or limiting cardiac injury and sport exercise safe for heart.Keywords: cardiac Troponin (cTn), high sensitivity cardiac troponin (hs-cTn), high intensity intensive exercise

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