Advancement of Mechanisms of Coxsackie Virus B3-Induced Myocarditis Pathogenesis and the Potential Therapeutic Targets

2019 ◽  
Vol 20 (14) ◽  
pp. 1461-1473 ◽  
Author(s):  
Tolessa Muleta Daba ◽  
Yue Zhao ◽  
Zhenwei Pan
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Treatment Options ◽  
Viral Myocarditis ◽  
Micro Rna ◽  
Biological Molecules ◽  
Coxsackie Virus ◽  
Chronic Myocarditis ◽  
Coxsackie Virus B3

Viral myocarditis is a cardiac disease caused by Group B Coxsackie virus of Enterovirus genus in the Picorna viridae family. It causes heart failure in children, young and adults. Ten Percent (10%) of acute heart failure and 12% of sudden deaths in young and adults who are less than 40 years is due to this viral myocarditis. If treatment action is not taken earlier, the viral disease can develop into chronic myocarditis and Dilated Cardiomyopathy which lead to congestive heart failure. And these eventually result in a reduced cardiac function which finally brings the victim to death. The only treatment option of the disease is heart transplantation once the acute stage of disease develops to chronic and Dilated Cardiomyopathy. Currently, there is a limitation in daily clinical treatments and even some available treatment options are ineffective. Therefore, focusing on search for treatment options through investigation is imperative. Recent studies have reported that biological molecules show a promising role. But their mechanism of pathogenesis is still unclear. A detailed study on identifying the role of biological molecules involved in Coxsackie B3 virus induced myocarditis and their mechanisms of pathogenesis; compiling and disseminating the findings of the investigation to the scientific communities contribute one step forward to the solution. Therefore, this review is aimed at compiling information from findings of current studies on the potential therapeutic role of micro RNA, cytokines and chemokines on the mechanism of pathogenesis of Coxsackie virus B3- induced myocarditis to give brief information for scholars to conduct a detailed study in the area.

Effects of Nano-α-Linolenic Acid and miR-146 on Mice with Viral Myocarditis

2021 ◽  
Vol 21 (2) ◽  
pp. 1365-1371
Author(s):  
Li Li ◽  
Mingjiang Zhong ◽  
Qiyu Zuo ◽  
Wenxue Ma ◽  
Zhigao Jiang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Linolenic Acid ◽  
Viral Myocarditis ◽  
The Body ◽  
Micro Rna ◽  
Dose Effect ◽  
Coxsackie Virus ◽  
Control Group ◽  
Coxsackie Virus B3

Micro RNA-146 (miR-146) is involved in mediating many innate and adaptive immune and inflammatory responses in the body. It is associated with a variety of systemic inflammation or autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and type 2 diabetes. In recent years, microRNAs (miRNAs) and nanotechnology have become research hotspots in cardiovascular pathology. The close relationship between host miRNAs and coxsackie virus B3 has gradually been discovered by scientists, which may provide new directions for the treatment and prevention of viral myocarditis. At the same time, recent studies have also found that nano-α-linolenic acid and its metabolites can inhibit the production of inflammatory cytokines such as TNF-α and IL-17; At the same time, they also have anti-lipid peroxidation effects. Therefore, in order to further explore the role of miR-146 and nano-α-linolenic acid in the occurrence and development of viral myocarditis, in this study, a mouse model of viral myocarditis was used to establish a VMC mouse model using coxsackie virus B3. Intervention with different doses of nano-α-linolenic acid, the control group was injected with the same amount of sodium chloride buffer, and the changes in cardiac function and inflammation indexes were compared to evaluate the role in the pathogenesis of viral myocarditis. The results showed that this study suggested that serum miR-146 concentration in viral myocarditis mice is increased and is positively correlated with serum IL-17 and TNF-α concentrations. This suggest that miR-146 in the circulation may be involved in the pathogenesis of viral myocarditis through IL-17 and TNF-α, providing a theoretical basis for the role of miR-146 in viral myocarditis, but its specific mechanism of action needs to be further studied. At the same time, the research in this experiment showed that nano-α-linolenic acid significantly improves the survival rate of CVB3 infected mice and reduces myocardial damage. And with the increase of the dosage of nano-α-linolenic acid, the effect is more significant, showing a significant dose-effect relationship.

scholarly journals Fructose and Mannose in Inborn Errors of Metabolism and Cancer

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 479
Author(s):  
Elizabeth L. Lieu ◽  
Neil Kelekar ◽  
Pratibha Bhalla ◽  
Jiyeon Kim
Keyword(s):  
Metabolic Disease ◽  
Inborn Errors Of Metabolism ◽  
Metabolic Diseases ◽  
Treatment Options ◽  
Biochemical Properties ◽  
Biological Molecules ◽  
Diagnostic Tools ◽  
Inborn Errors ◽  
Mannose Metabolism

History suggests that tasteful properties of sugar have been domesticated as far back as 8000 BCE. With origins in New Guinea, the cultivation of sugar quickly spread over centuries of conquest and trade. The product, which quickly integrated into common foods and onto kitchen tables, is sucrose, which is made up of glucose and fructose dimers. While sugar is commonly associated with flavor, there is a myriad of biochemical properties that explain how sugars as biological molecules function in physiological contexts. Substantial research and reviews have been done on the role of glucose in disease. This review aims to describe the role of its isomers, fructose and mannose, in the context of inborn errors of metabolism and other metabolic diseases, such as cancer. While structurally similar, fructose and mannose give rise to very differing biochemical properties and understanding these differences will guide the development of more effective therapies for metabolic disease. We will discuss pathophysiology linked to perturbations in fructose and mannose metabolism, diagnostic tools, and treatment options of the diseases.

scholarly journals Dapagliflozin Alleviates Myocardial Inflammation by Regulating the Macrophage Polarization and Stat3-related Pathways in Coxsackie Virus B3-induced Acute Viral Myocarditis

2022 ◽  
Author(s):  
Pengcheng Yan ◽  
Xiaoning Song ◽  
Joanne Tran ◽  
Runfa Zhou ◽  
Xinran Cao ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Viral Myocarditis ◽  
Coxsackie Virus ◽  
Myocardial Inflammation ◽  
Protective Effects ◽  
Acute Viral Myocarditis ◽  
Cvb3 Infection ◽  
Coxsackie Virus B3

Abstract Viral myocarditis (VMC), which is most prevalently caused by Coxsackievirus B3 (CVB3) infection, is a serious clinical condition characterized by cardiac inflammation. Dapagliflozin, a kind of sodium glucose co-transporters 2(SGLT-2) inhibitor, exhibited protective effects on plenty of inflammatory diseases, while its effect on viral myocarditis has not been studied. Recently we found the protective effect of dapagliflozin on VMC. After CVB3 infection, dapagliflozin were given orally to Balb/c male mice for 8 days and then the severity of myocarditis was assessed. Our results indicated that dapagliflozin significantly alleviated the severity of viral myocarditis, elevated the survival rate, and ameliorated cardiac function. Besides, dapagliflozin can decrease the level of proinflammatory cytokines included IL-1β, IL-6, TNF-α. Furthermore, dapagliflozin can inhibit macrophages differentiate to classically activated macrophages (M1) in cardiac tissue and activate the Stat3 signal pathway which is reported to promote polarization of the alternatively activated macrophage (M2). In conclusion, our study demonstrates that dapagliflozin alleviates myocardial inflammation by regulating the macrophage polarization and Stat3-related pathways in coxsackie virus B3-induced acute viral myocarditis.

Abstract 88: A Crucial Role of BAG3 in Preventing Dilated Cardiomyopathy

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Xi Fang ◽  
Julius Bogomolovas ◽  
Wei Zhang ◽  
Tongbin Wu ◽  
Canzhao Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Protein Quality ◽  
Contractile Function ◽  
Metabolic Stress ◽  
Insoluble Fraction ◽  
Therapeutic Benefit ◽  
Loss Of Function ◽  
Specific Subset

Defective protein quality control (PQC) systems are implicated in multiple diseases, with molecular chaperones/co-chaperones being critical to PQC. Cardiomyocytes are constantly challenged by mechanical and metabolic stress, placing great demand on the PQC system. Mutations and downregulation of the co-chaperone protein B cl-2- a ssociated athano g ene 3 (BAG3) are associated with cardiac myopathy and heart failure, and a BAG3 E455K mutation leads to Dilated cardiomyopathy (DCM). However, the role of BAG3 in the heart and mechanisms by which the E455K mutation lead to DCM remained obscure. Here, we found that cardiac-specific BAG3 knockout (CKO) and cardiac-specific E455K BAG3 knockin mice developed DCM. Comparable phenotypes in the two mutants demonstrated that the E455K mutation resulted in loss-of-function, and experiments revealed that the E455K mutation disrupted interaction between BAG3 and HSP70. In both mutants, decreased levels of small heat shock proteins (sHSPs) were observed, and a specific subset of proteins required for metabolic and contractile function of cardiomyocytes was enriched in the insoluble fraction. Together, these observations suggested that interaction between BAG3 and HSP70 was essential for BAG3 to stabilize sHSPs and maintain cardiomyocyte protein homeostasis. Our results provide new insight into the pathogenesis of heart failure caused by defects in BAG3 pathways, suggesting that increasing protein levels of BAG3 may be of therapeutic benefit in heart failure.

scholarly journals The Role of Cardiac T-Cadherin in the Indicating Heart Failure Severity of Patients with Non-Ischemic Dilated Cardiomyopathy

Medicina ◽  
2020 ◽  
Vol 56 (1) ◽  
pp. 27
Author(s):  
Vaida Baltrūnienė ◽  
Ieva Rinkūnaitė ◽  
Julius Bogomolovas ◽  
Daiva Bironaitė ◽  
Ieva Kažukauskienė ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Experimental Studies ◽  
Left Ventricular ◽  
Human Myocardium ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cox Regression Analysis ◽  
Non Ischemic Dilated Cardiomyopathy ◽  
The Mean

Background and objectives: T-cadherin (T-cad) is one of the adiponectin receptors abundantly expressed in the heart and blood vessels. Experimental studies show that T-cad sequesters adiponectin in cardiovascular tissues and is critical for adiponectin-mediated cardio-protection. However, there are no data connecting cardiac T-cad levels with human chronic heart failure (HF). The aim of this study was to assess whether myocardial T-cad concentration is associated with chronic HF severity and whether the T-cad levels in human heart tissue might predict outcomes in patients with non-ischemic dilated cardiomyopathy (NI-DCM). Materials and Methods: 29 patients with chronic NI-DCM and advanced HF were enrolled. Patients underwent regular laboratory investigations, echocardiography, coronary angiography, and right heart catheterization. TNF-α and IL6 in serum were detected by enzyme-linked immunosorbent assay (ELISA). Additionally, endomyocardial biopsies were obtained, and the levels of T-cad were assessed by ELISA and CD3, CD45Ro, CD68, and CD4- immunohistochemically. Mean pulmonary capillary wedge pressure (PCWP) was used as a marker of HF severity, subdividing patients into two groups: mean PCWP > 19 mmHg vs. mean PCWP < 19 mmHg. Patients were followed-up for 5 years. The study outcome was composite: left ventricular assist device implantation, heart transplantation, or death from cardiovascular causes. Results: T-cad shows an inverse correlation with the mean PCWP (rho = −0.397, p = 0.037). There is a tendency towards a lower T-cad concentration in patients with more severe HF, as indicated by the mean PCWP > 19 mmHg compared to those with mean PCWP ≤ 19 mmHg (p = 0.058). Cardiac T-cad levels correlate negatively with myocardial CD3 cell count (rho = −0.423, p = 0.028). Conclusions: Univariate Cox regression analysis did not prove T-cad to be an outcome predictor (HR = 1, p = 0.349). However, decreased T-cad levels in human myocardium can be an additional indicator of HF severity. T-cad in human myocardium has an anti-inflammatory role. More studies are needed to extend the role of T-cad in the outcome prediction of patients with NI-DCM.

scholarly journals Distinct different expression of Th17 and Th9 cells in coxsackie virus B3-induced mice viral myocarditis

2011 ◽  
Vol 8 (1) ◽  
pp. 267 ◽  
Author(s):  
Kong Qing ◽  
Wu Weifeng ◽  
Yang Fan ◽  
Yan Yuluan ◽  
Pang Yu ◽  
...  
Keyword(s):  
Viral Myocarditis ◽  
Coxsackie Virus ◽  
Th9 Cells ◽  
Coxsackie Virus B3

scholarly journals Comparative analysis of structural and functional heart state in patients with chronic myocarditis and dilated cardiomyopathy

2019 ◽  
Vol 26 (1) ◽  
pp. 72-78
Author(s):  
V. M. Kovalenko ◽  
E. G. Nesukay ◽  
S. V. Cherniuk ◽  
I. I. Giresh ◽  
N. S. Titova ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ventricular Tachycardia ◽  
Comparative Analysis ◽  
Dilated Cardiomyopathy ◽  
Functional State ◽  
Left Ventricular ◽  
Functional Class ◽  
Imaging Results ◽  
Chronic Myocarditis ◽  
Lower Tolerance

The aim – to establish differences in the structural and functional state of the heart in patients with chronic myocarditis and dilated cardiomyopathy and to investigate their associations with the presence of cardiac rhythm disorders. Materials and methods. We included 95 patients who were divided into two groups: the first group consisted of 55 patients with chronic myocarditis (CM), the second group included 40 patients with dilated cardiomyopathy (DCM). All patients had heart failure (HF) II or higher functional class (FC) according to the classification of the New York Heart Association (NYHA) and a reduced left ventricular (LV) ejection fraction (EF). All patients underwent the echocardiography (EchoCG) with speckle tracking (ST), Holter electrocardiogram monitoring and cardiac magnetic resonance (CMR) imaging. Results and discussion. A comparative analysis of the EchoCG data revealed that CM was characterized by lower values of LV end-diastolic and end-systolic volume indexes (by 21.7 and 28.6 %, respectively, p<0.01) and by 16.8 % (p<0.05) higher value of LV EF compared to DCM; when studying the results of ST EchoCG, it was found that in patients with CM, the absolute values of the longitudinal, circumferential and radial global systolic LV strain were by 25.0; 23.7 and 28.5 %, respectively, higher compared with patients with DCM (p<0.05–0.01). The obtained data were confirmed by the results of 6-minute walking test, so patients with DCM demonstrated the lower tolerance to physical exercise comparing with CM. When performing CMR in patients with CM, along with inflammatory changes in the myocardium (edema and hyperemia), fibrotic changes were present, while DCM was characterized only by diffuse fibrotic changes of the heart. The association between the presence of delayed enhancement on CMR and episodes of unstable ventricular tachycardia was proved for both CM and DCM – the result of Fisher’s exact test was p=0.019 and p=0.027 respectively. Conclusions. In patients with DCM compared with CM we found more significant impairment of the structural and functional state of the heart, that was manifested by the presence of the worst heart failure functional class and a lower tolerance to exercise test. It has been established that fibrotic changes of the myocardium both in CM and in DCM are associated with the presence of ventricular arrhythmias, including such potentially dangerous ones as episodes of unstable ventricular tachycardia.

Sign in / Sign up

Export Citation Format

Share Document