scholarly journals Galectin-Receptor Interactions Regulates Cardiac Pathology Caused by Trichinella spiralis Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinghai Yan ◽  
Shiguang Huang ◽  
Fangli Lu
Keyword(s):  
Cardiac Fibrosis ◽  
Trichinella Spiralis ◽  
Eosinophil Cationic Protein ◽  
Myocardial Damage ◽  
Eosinophil Infiltration ◽  
Mrna Levels ◽  
Cationic Protein ◽  
Receptor Interactions ◽  
Heart Pathology ◽  
The Impact

The parasitic nematode Trichinella spiralis causes trichinellosis, a serious food-borne parasitic zoonosis worldwide. Infection with T. spiralis may also cause myocarditis. In the present study, we used mouse models to assess the impact of blockage of galectin-receptor interactions by α-lactose on cardiac immunopathology during acute T. spiralis experimental infection. Our data demonstrated that, after T. spiralis infection, blockage of galectin-receptor interactions resulted in cardiac dysfunction detected by transthoracic conventional echocardiography, and increased serum Gal-3 level, a biomarker of myocardial damage. In addition, there were increased eosinophil number in peripheral blood, and increased eosinophil infiltration in the heart and spleen tissues accompanied with increased mRNA levels of eosinophil granule proteins (including eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO)) and IL-5 in these organs; increased cardiac fibrosis accompanied with increased Gal-3 and collagen 1 expressions in the hearts of mice with blockage of galectin-receptor interactions after T. spiralis infection. Correlation analysis showed that significant positive correlations existed between the mRNA levels of Gal-3 and ECP/EPO/eosinophil major basic protein/IL-5/CCL11/CCR3/α-SMA/collagen 1 in the hearts of both T. spiralis-infected mice and T. spiralis-infected mice with blockage of galectin-receptor interactions. Our data suggest that galectin-receptor interactions play a pivotal role during acute T. spiralis infection, and lack of galectin-receptor interactions upregulates Gal-3 which, in turn, leads to elevated heart eosinophil recruitment, exacerbated heart pathology and fibrosis, and heart functional damage.

scholarly journals Effects of human eosinophil granule-derived cationic proteins on C-fiber afferents in the rat lung

2001 ◽  
Vol 91 (3) ◽  
pp. 1318-1326 ◽  
Author(s):  
Lu-Yuan Lee ◽  
Qihai Gu ◽  
Gerald J. Gleich
Keyword(s):  
Eosinophil Cationic Protein ◽  
Eosinophil Infiltration ◽  
Cationic Protein ◽  
Human Eosinophil ◽  
Lung Inflation ◽  
Cationic Proteins ◽  
C Fibers ◽  
Arterial Blood ◽  
C Fiber ◽  
Eosinophil Granule

Experiments were performed to test the hypothesis that human eosinophil granule-derived cationic proteins stimulate vagal C-fiber afferents in the lungs and elicit pulmonary chemoreflex responses in anesthetized Sprague-Dawley rats. Intratracheal instillation of eosinophil cationic protein (ECP; 1–2 mg/ml, 0.1 ml) consistently induced an irregular breathing pattern, characterized by tachypnea (change in breathing frequency of 44.7%) and small unstable tidal volume (Vt). The tachypnea, accompanied by decreased heart rate and arterial blood pressure, started within 30 s after the delivery of ECP and lasted for >30 min. These ECP-induced cardiorespiratory responses were completely prevented by perineural capsaicin treatment of both cervical vagi, which selectively blocked C-fiber conduction, suggesting the involvement of these afferents. Indeed, direct recording of single-unit activities of pulmonary C-fibers further demonstrated that the same dose of ECP evoked a pronounced and sustained (>30-min) stimulatory effect on pulmonary C-fibers. Furthermore, the sensitivity of these afferents to lung inflation was also markedly elevated after the ECP instillation, whereas the vehicle of ECP administered in the same manner had no effect. Other types of eosinophil granule cationic proteins, such as major basic protein and eosinophil peroxidase, induced very similar respiratory and cardiovascular reflex responses. In conclusion, these results show that eosinophil granule-derived cationic proteins induce a distinct stimulatory effect on vagal pulmonary C-fiber endings, which may play an important role in the airway hyperresponsiveness associated with eosinophil infiltration in the airways.

scholarly journals BMP7 Ameliorated Viral Myocardial Fibrosis by Inhibiting Endothelial-to-Mesenchymal Transition

2020 ◽  
Author(s):  
Yeqing Xie ◽  
Jianquan Liao ◽  
Yong Yu ◽  
Ruizhen Chen ◽  
Xiaoqiang Ding
Keyword(s):  
Myocardial Fibrosis ◽  
Cardiac Fibrosis ◽  
Viral Myocarditis ◽  
Myocardial Damage ◽  
Mrna Levels ◽  
Mesenchymal Transition ◽  
Protein Levels ◽  
Cvb3 Infection ◽  
Endothelial To Mesenchymal Transition

Abstract Background: Endothelial-to-mesenchymal transition (Endo-MT) is associated with myocardial fibrosis in dilated cardiomyopathy (DCM). Endothelial-to-mesenchymal transition (Endo-MT) is induced by coxsackievirus B3 (CVB3) in cardiac microvascular endothelial cells (CMVECs). Bone morphogenetic protein 7 (BMP7) significantly inhibits Endo-MT and the progression of cardiac fibrosis. The study was aimed to investigate the effect and the underlying mechanism of BMP7 on Endo-MT in myocardial fibrosis induce by CVB3 infection in vivo. Methods: BALB/c mice were intraperitoneally injected by CVB3 to induce viral myocarditis (VMC). Mice were treated with BMP7 after CVB3 infection. Subsequently, all groups of mice were determined by echocardiography, histopathologic and molecular detection. Results: We found that the ratio of BMP7/TGF-β1 in mRNA levels was decreased obviously at different time points after CVB3 injection. BMP7 facilitated the recovery of cardiac function after CVB3 infection via inhibition of myocardial damage, collagen deposition. Double immunofluorescence staining indicated that Endo-MT was implicated in CVB3-induced myocardial fibrosis, which was attenuated by BMP7. The protein levels of pSmad3 and Smad4 were significantly upregulated in VMC group, as well as Wnt/β-catenin and the transcription factor snail. BMP7 treatment reversed the changes of these protein levels. Moreover, CO-IP demonstrated the crosstalk between β-catenin and Smad3 in VMC mice, which was downregulated by BMP7 treatment. Conclusions: These results indicated that BMP7 obviously ameliorated myocardial fibrosis in CVB3-infected mice via Endo-MT, which was involved in the TGF-β/Smad and Wnt/β-catenin pathway. β-Catenin/Smad3 interaction may be associated with Endo-MT in the development of viral myocardial fibrosis.

scholarly journals The kinetics of allergen-induced transcription of messenger RNA for monocyte chemotactic protein-3 and RANTES in the skin of human atopic subjects: relationship to eosinophil, T cell, and macrophage recruitment.

1995 ◽  
Vol 181 (6) ◽  
pp. 2153-2159 ◽  
Author(s):  
S Ying ◽  
L Taborda-Barata ◽  
Q Meng ◽  
M Humbert ◽  
A B Kay
Keyword(s):  
T Cells ◽  
Messenger Rna ◽  
Eosinophil Cationic Protein ◽  
Allergen Challenge ◽  
Eosinophil Infiltration ◽  
Cationic Protein ◽  
Monocyte Chemotactic Protein ◽  
Chemotactic Protein ◽  
Kinetics Of

The C-C chemokines RANTES and monocyte chemotactic protein-3 (MCP-3) are potent chemoattractants in vitro for eosinophils and other cell types associated with allergic reactions. We tested the hypothesis that the allergen-induced infiltration of eosinophils, T cells, and macrophages in the skin of atopic subjects is accompanied by the appearance of mRNA+ cells for RANTES and MCP-3. Cryostat sections were obtained from skin biopsies from six subjects 6, 24, and 48 h after allergen challenge. Tissue was processed for immunocytochemistry (ICC) and for in situ hybridization using 35S-labeled riboprobes for RANTES and MCP-3. In contrast to diluent controls, allergen provoked a significant increase in mRNA+ cells for MCP-3, which peaked at 6 h and progressively declined at 24 and 48 h. This paralleled the kinetics of total (major basic protein positive [MBP]+) and activated (cleaved form of eosinophil cationic protein [EG2]+) eosinophil infiltration. The allergen-induced expression of cells mRNA+ for RANTES was also clearly demonstrable at 6 h. However, the numbers were maximal at 24 h and declined slightly at the 48-h time point. The number of mRNA+ cells for RANTES paralleled the kinetics of infiltration of CD3+, CD4+, and CD8+ T cells whereas the number of CD68+ macrophages was still increasing at 48 h. These data support the view that MCP-3 is involved in the regulation of the early eosinophil response to specific allergen, whereas RANTES may have more relevance to the later accumulation of T cells and macrophages.

scholarly journals Synthesis of interleukin-5 by activated eosinophils in patients with eosinophilic heart diseases

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1553-1560 ◽  
Author(s):  
P Desreumaux ◽  
A Janin ◽  
S Dubucquoi ◽  
MC Copin ◽  
G Torpier ◽  
...  
Keyword(s):  
Heart Diseases ◽  
Elevated Serum ◽  
Eosinophil Cationic Protein ◽  
Eosinophil Infiltration ◽  
Cationic Protein ◽  
Interleukin 5 ◽  
Eosinophil Granule Proteins ◽  
Eosinophil Activation ◽  
Granule Proteins ◽  
Eosinophil Granule

Abstract Eosinophilic endomyocardial disease represents a major evolutive risk in chronic eosinophilia-associated disorders. Eosinophil granule proteins appear to be involved in cardiac injury, but the mechanisms leading to eosinophil infiltration and degranulation are not clear. Interleukin-5 (IL-5) has been recently shown to be produced by eosinophils and might play a role in both chemoattraction and degranulation of eosinophils. In four cases of eosinophilic diseases with severe cardiac failure, we evaluated the proportion of eosinophil phenotypes and the serum levels of eosinophil cationic protein (ECP) and soluble IL-2 receptor (sIL-2R), markers of disease activity in the hypereosinophilic syndromes. All four patients showed a markedly increased proportion of hypodense eosinophils with elevated serum ECP and sIL-2R levels. In all four patients, extracellular deposition of eosinophil granule proteins and features of eosinophil activation were observed in cardiac tissues. The synthesis of IL-5 by eosinophils was detected in myocardial sections and blood cells by in situ hybridization and by immunostaining with a monoclonal antibody against human IL-5. Sixty percent to 90% of tissue eosinophils expressed IL-5 mRNA and IL-5 protein. These data suggest that IL-5 can be produced by eosinophils at the sites of myocardial tissue damage and might participate in local eosinophil activation.

scholarly journals Multimodality Imaging in Ischemic Cardiomyopathy

2019 ◽  
Vol 71 (1) ◽  
pp. 1-4
Author(s):  
Florina Bolea Batar ◽  
Gabriela Eminovici ◽  
Andra-Maria Bebeselea ◽  
Ioan Manitiu
Keyword(s):  
Heart Function ◽  
Multimodality Imaging ◽  
Imaging Techniques ◽  
Myocardial Damage ◽  
Left Ventricular ◽  
Imaging Method ◽  
Heart Pathology ◽  
The Moment ◽  
The Impact ◽  
Myocardium Injury

Abstract Ischemic heart disease is the most common heart pathology in medical practice. Proper assessment of the size of myocardium injury and its consequences on the heart function is extremely important both for a correct drug therapy and for interventional approach. Most frequently the left ventricle is affected. The need for accurate evaluation of the impact of left ventricular myocardial damage has led to the development of new imaging techniques and improvement of the existing ones. At the moment the most commonly used imaging method for the assessment of left ventricular function is echocardiography. Cardiac Magnetic Resonance and nuclear tomography are precious imaging techniques as well. They are more expensive but bring valuable information when used in adequate situations.

scholarly journals Synthesis of interleukin-5 by activated eosinophils in patients with eosinophilic heart diseases

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1553-1560 ◽  
Author(s):  
P Desreumaux ◽  
A Janin ◽  
S Dubucquoi ◽  
MC Copin ◽  
G Torpier ◽  
...  
Keyword(s):  
Heart Diseases ◽  
Elevated Serum ◽  
Eosinophil Cationic Protein ◽  
Eosinophil Infiltration ◽  
Cationic Protein ◽  
Interleukin 5 ◽  
Eosinophil Granule Proteins ◽  
Eosinophil Activation ◽  
Granule Proteins ◽  
Eosinophil Granule

Eosinophilic endomyocardial disease represents a major evolutive risk in chronic eosinophilia-associated disorders. Eosinophil granule proteins appear to be involved in cardiac injury, but the mechanisms leading to eosinophil infiltration and degranulation are not clear. Interleukin-5 (IL-5) has been recently shown to be produced by eosinophils and might play a role in both chemoattraction and degranulation of eosinophils. In four cases of eosinophilic diseases with severe cardiac failure, we evaluated the proportion of eosinophil phenotypes and the serum levels of eosinophil cationic protein (ECP) and soluble IL-2 receptor (sIL-2R), markers of disease activity in the hypereosinophilic syndromes. All four patients showed a markedly increased proportion of hypodense eosinophils with elevated serum ECP and sIL-2R levels. In all four patients, extracellular deposition of eosinophil granule proteins and features of eosinophil activation were observed in cardiac tissues. The synthesis of IL-5 by eosinophils was detected in myocardial sections and blood cells by in situ hybridization and by immunostaining with a monoclonal antibody against human IL-5. Sixty percent to 90% of tissue eosinophils expressed IL-5 mRNA and IL-5 protein. These data suggest that IL-5 can be produced by eosinophils at the sites of myocardial tissue damage and might participate in local eosinophil activation.

Abstract 272: The Orphan Receptor GPRC5B Increases Pro-Inflammatory Signaling in Neonatal Rat Cardiac Fibroblasts and Cardiac MMP-9-expression in vivo

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Friedrich A von Samson-Himmelstjerna ◽  
Greta Freundt ◽  
Norbert Frey ◽  
Hans-Joerg Hippe
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Orphan Receptor ◽  
Neonatal Rat ◽  
Myocardial Inflammation ◽  
Mouse Heart ◽  
Mrna Levels ◽  
Protein Levels ◽  
Cellular Inflammatory Response ◽  
The Impact

Background: Inflammatory processes driven by cardiac fibroblasts (CF) play a major role in cardiac fibrosis and eventually diastolic dysfunction leading to heart failure. GPRC5B, a novel G protein-coupled orphan receptor, is involved in inflammatory pathways in adipocytes and endogenously expressed in CF. Hypothesis: We assessed the impact of GPRC5B on inflammatory and fibrotic pathways in isolated neonatal rat CF and mouse heart. Methods & Results: We show that 48h-stimulation of CF with Tumor Necrosis Factor α (TNFα, 50ng/ml) or Lipopolysaccharides (LPS, 100ng/ml) leads to a significant up-regulation of GPRC5B protein levels compared to unstimulated cells (TNFα +74%, p<0.01; LPS +111%, p<0.001, n=8) . This is confirmed by evaluation of mRNA levels after 12h-stimulation ( TNFα +69%, p<0.01; LPS +61%, p<0.01, n=9) . Similarly, a mechanical stretch of 18% of CF length for 24h increases GPRC5B-mRNA by 83% (p<0.01, n=6). Adenoviral overexpression of GPRC5B results in an increased TNFα- ( +84%, p<0.01) , Interleukin 1ß- (IL1ß, +56%, p<0.05 ), Interleukin 6- (IL6, +32%, p<0.05 ) and Matrix-Metalloproteinase 9- (MMP9, +133%, p<0.01 ) mRNA production in CF ( AdLacZ vs. AdGPRC5B, n=9) . After an additional 24h-stimulation with LPS (10ng/ml), IL1ß-, IL6- and MMP9-mRNA increases as compared to AdLacZ-infected control cells ( AdLacZ+LPS vs. AdGPRC5B+LPS : IL1ß +114%, p<0.01; IL6 +113%, p<0.05; MMP9 +195%, p<0.01; n=8). Conversely, siRNA mediated knockdown to 25% of endogenous protein levels followed by 24h-stimulation with LPS (10ng/ml) lowers significantly the expression of TNFα-, IL1ß- and IL6-mRNA when compared to control-transfected cells (siNeg+LPS vs. siGPRC5B+LPS: TNFα -28%, p<0.05; IL1ß -30%, p<0.05; MMP9 -34%, p<0.05; n=8). These findings are supported by Western Blot analysis of heart tissue from GPRC5B-transgenic mice revealing an increased protein expression of MMP9 in contrast to wild type mice (WT vs. GPRC5B-TG: MMP9 +60%, p<0.001; n=10). Conclusion: GPRC5B is up-regulated in cardiac models of inflammation and mechanical stress. GPRC5B modulates cellular inflammatory response by increasing the levels of key cytokines in CF and of MMP9 expression in mouse heart pointing to a role in myocardial inflammation and cardiac remodeling.

scholarly journals MiR-22 may Suppress Fibrogenesis by Targeting TGFβR I in Cardiac Fibroblasts

2016 ◽  
Vol 40 (6) ◽  
pp. 1345-1353 ◽  
Author(s):  
Yuan Hong ◽  
Huaming Cao ◽  
Qiang Wang ◽  
Jianlin Ye ◽  
Lijun Sui ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Angiotensin Ii ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Coronary Artery Occlusion ◽  
Negative Regulator ◽  
Luciferase Assay ◽  
Mrna Levels ◽  
Collagen Formation ◽  
The Impact

Background/Aims: Cardiac fibrosis after myocardial infarction (MI) has been identified as a key factor in the development of heart failure, but the mechanisms undelying cardiac fibrosis remained unknown. microRNAs (miRNAs) are novel mechanisms leading to fibrotic diseases, including cardiac fibrosis. Previous studies revealed that miR-22 might be a potential target. However, the roles and mechanisms of miR-22 in cardiac fibrosis remained ill defined. The present study thus addressed the impact of miR-22 in cardiac fibrosis. Methods: After seven days following coronary artery occlusion in mice, tissues used for histology were collected and processed for Masson's Trichrome staining. In addition, cardiac fibroblasts were transfected with mimics and inhibitors of miR-22 using Lipofectamin 2000, and luciferase activity was measured in cell lysates using a luciferase assay kit. Western blotting was used to detect the expression of collagen1, α-SMA and TGFβRI proteins levels, and real time-PCR was employed to measure the Col1α1, Col3α1, miR-22 and TGFβRI mRNA levels. Results: In this study, we found that miR-22 was dynamically downregulated following MI induced by permanent ligation of the left anterior descending coronary artery for 7 days, an effect paralleled by significant collagen deposition. Inhibition of miR-22 with AMO-22 resulted in increased expression of Col1α1, Col3α1 and fibrogenesis in cultured cardiac fibroblasts. Conversely, overexpression of miR-22 in cultured cardiac fibroblasts significantly abrogated angiotensin II-induced collagen formation and fibrogenesis. Furthermore, we found that TGFβRI is a direct target for miR-22, and downregulation of TGFβR may have mediated the antifibrotic effect of miR-22. Conclusion: Our data clearly demonstrate that miR-22 acts as a novel negative regulator of angiotensin II-induced cardiac fibrosis by suppressing the expression of TGFβRI in the heart and may represent a new potential therapeutic target for treating cardiac fibrosis.

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