OBJECTIVE: To study the pathogenesis of viral myocarditis (VMC) and dilated cardiomyopathy (DCM) and their relationship. METHODS: Sixty samples including 20 VMC, 20 DCM and 20 controls were collected. The expression of Fas protein in myocardium of each group was detected by modified immunohistochemistry with unequivocal brown staining in the myocardial membrane scored as positive, and the results of positive reaction were analyzed by Ridit test. RESULTS: Fas protein expression increased obviously in VMC and DCM groups as compared with that of the control group. The difference of positive results between each group analyzed by Ridit test was statistically significant (P<0.005). Statistically significant differences were found between VMC and control groups as well as between DCM and control groups (P<0.05), but not between VMC and DCM groups (P>0.05) by multiple comparison Ridit test. CONCLUSION The expression of Fas protein is significantly higher in the VMC and DCM groups than in that of the control group. These results suggest that both the VMC and DCM may share a similar pathogenesis, which most likely involves cell apoptosis.
Apoptosis/physiology* ; Cardiomyopathy, Dilated/pathology* ; Case-Control Studies ; Female ; Forensic Pathology ; Humans ; Male ; Myocarditis/virology* ; fas Receptor/metabolism*

OBJECTIVE: In order to improve the accuracy and reliability in sudden cardiac death, the pathogenesis and relationship between the viral myocarditis and dilated cardiomyopathy were investigated. METHODS: Improved immunohistochemical technique was adopted to detect the expression of the dystrophin in myocardium from 25 viral myocarditis, 28 dilated cardiomyopathy and 17 control cases including normal, coronary atherosclerotic heart disease and hypertension heart disease as control. RESULTS: The positive rate of dystrophin protein expression in control group was 100%, that in viral myocarditis was 88%, and that in dilated cardiomyopathy was 57%, There were significant differences among three groups (P<0.05), and the correlation between viral myocarditis and dilated cardiomyopathy group (r = -0.526)were also found. CONCLUSION The myocardial cytoskeletal protein is disrupted in viral myocarditis and dilated cardiomyopathy, and the dystrophin protein may be involved in the pathogenesis of viral myocarditis and dilated cardiomyopathy. The viral infect and impair heart functions by cleaving host dystrophin proteins may ultimately contributes to the viral myocarditis to the converting from dilated cardiomyopathy.
Cardiomyopathy, Dilated/metabolism* ; Case-Control Studies ; Death, Sudden, Cardiac ; Dystrophin/metabolism* ; Enterovirus Infections/complications* ; Female ; Humans ; Immunohistochemistry ; Male ; Myocarditis/virology* ; Myocardium/pathology* ; Staining and Labeling

OBJECTIVE: To explore etiology and pathogenesis of viral myocarditis (VMC) and dilated cardiomyopathy (DCM). METHODS: The expression of Coxsackie B virus and adenovirus receptors (CAR) were detected with modified immunohistochemical (IHC) technique in myocardium of left ventricle, right ventricle, interventricular septum, and septal papillary muscle from 28 patients with viral myocarditis, 31 patients with dilated cardiomyopathy and 17 control patients (including normal, hypertension heart disease, myocardial infarction and coronary atherosclerotic heart disease). RESULTS: The brown staining on the cell membrane of myocardium represents positive result. 100% (28 of 28) of VMC patients (IHC surface integral: 4.3975 +/- 0.0365) and 84% (26 of 31) of DCM patients (4.2064 +/- 0.052 6) had prevalent CAR expression compared to 0% (0 of 19) control patients (0.073 1 +/- 0.0362). There were statistically significant differences between VMC/DCM and control patients (P < 0.05). CONCLUSION The prevalence of CAR expression was significantly higher in VMC and DCM patients (100% and 84% vs. 0% in control). In contrast, there was no difference found between VMC and DCM patients. These results suggest that both VMC and DCM involve viral etiology and could share a similar pathogenesis.
Adenovirus Infections, Human/complications* ; Cardiomyopathy, Dilated/virology* ; Case-Control Studies ; Coxsackie and Adenovirus Receptor-Like Membrane Protein ; Coxsackievirus Infections/complications* ; Death, Sudden, Cardiac ; Female ; Humans ; Immunohistochemistry ; Male ; Myocarditis/virology* ; Myocardium/pathology* ; Receptors, Virus/metabolism*

OBJECTIVETo investigate the correlations among persistent viral infection, heart function and Chinese medicine (CM) difined-syndromes in patients with dilated cardiomyopathy (DCM).

METHODSFifty patients with DCM in the First Affiliated Hospital of Zhejiang Chinese Medical University from October 2009 to December 2011 were selected as the research subjects, and 30 healthy people were simultaneously selected as the normal control group to detect persistent viral infections after admission. The CM syndrome type and grade of heart function were then evaluated. The expression level of Coxsackie adenovirus receptor (CAR) was detected using the flow cytometry (FCM) technique, coxsackie virus RNA (CVB-RNA) using reverse transcription polymerase chain reaction (RTPCR), and the plasma brain natriuretic peptide (BNP) level with a Triage meter plus diagnosis instrument. Finally, the parameters such as left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by ultrasonic cardiogram. Person correlation analysis was used for measured data, Spearman correlation analysis for rating data, and the Chi-square test for numerical data.

RESULTSCVB-RNA was positive in 22 patients (44%) with DCM, while only 6 cases (20%) were CVB-RNA-positive in the normal control group, with a significant difference between the two groups (P<0.01). The expression level of CAR was significantly elevated in the DCM group compared with the normal control group (P<0.01). In CVB-RNA-positive patients (22 cases), the expression level of CAR was significantly higher than in CVB-RNA-negative patients (28 cases; P<0.01). In the DCM patients, there was a positive correlation between the CAR expression and the BNP level (r=0.34, P<0.05), while no significant difference was found between the CAR expression and the LVEF and LVEDd (r=-0.32, 0.30, P>0.05). There was no clear correlation between virus infection and the CM syndrome types in DCM patients (r=-0.22, P>0.05). According to the sequence of syndrome types: phlegm → qi deficiency → blood stasis → hydroretention with asthenic yang (from low to high), a positive correlation was existed between the BNP levels and CM syndrome types (r=0.139, P<0.05).

CONCLUSIONThe expression of CAR on the surface of white cells could be used to detect persistent viral infection. The expression level of CAR and heart function in DCM patients were highly correlated. The expression level of BNP may serve as an objective index for differentiating CM syndromes for patients with DCM.

Adult ; Aged ; Cardiomyopathy, Dilated ; blood ; complications ; physiopathology ; virology ; Coxsackie and Adenovirus Receptor-Like Membrane Protein ; Coxsackievirus Infections ; blood ; complications ; physiopathology ; Female ; Heart Function Tests ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; RNA, Viral ; blood ; Syndrome

OBJECTIVETo explore the role of interleukin-17 (IL-17) in the evolution of viral myocarditis (VMC) into dilated cardiomyopathy (DCM).

METHODSA mouse model of VMC was established in 100 male Balb/c mice by intraperitoneal injection of coxsackievirus B3. The expression of IL-17 protein in the cardiac tissue of the mice was detected immunohistochemically, and IL-17 mRNA in the splenocytes was examined by reverse transcription-polymerase chain reaction (RT-PCR). IL-17 levels in the plasma, peripheral blood mononuclear cell (PBMC) culture supernatants, and phytohemagglutinin (PHA)-stimulated PBMC culture supernatants were measured in 30 DCM patients, 26 non-DCM patients and 20 normal adults using enzyme-linked immunosorbent assay (ELISA), and IL-17 mRNA expression in the PBMCs was detected using RT-PCR.

RESULTSThe levels of IL-17 mRNA in the splenocytes of the mice with VMC were significantly higher at 4 and 6 weeks than those at 8 weeks (P<0.01), but not detected at 2 weeks. No IL-17 expression was found in the ventricular tissue of the mice at 2 weeks, but peaked at 4 weeks followed by gradual decrease (P<0.01). IL-17 level in PHA-stimulated PBMC culture supernatants but not the plasma, and its mRNA level in PHA-stimulated PBMCs but not the PBMC culture supernatants, were significantly elevated in DCM patients as compared with those in non-DCM patients and normal control subjects.

CONCLUSIONSThe mouse model of VMC in the chronic phase and DCM patients express high levels of IL-17, which may contribute to the transition from VMC to DCM.

Adult ; Animals ; Cardiomyopathy, Dilated ; etiology ; metabolism ; pathology ; Coxsackievirus Infections ; complications ; metabolism ; Enterovirus B, Human ; Female ; Humans ; Interleukin-17 ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Myocarditis ; complications ; metabolism ; virology ; RNA, Messenger ; genetics ; metabolism

OBJECTIVE: In order to improve accuracy and reliability of forensic diagnosis of sudden cardiac death, pathogenesis and relationship between the viral myocarditis (VMC) and dilated cardiomyopathy (DCM) were investigated. METHODS: Improved immunohistochemical technique was used to detect the expression of the CAR in myocardium samples, including 22 deceased with VMC, 20 deceased with DCM and 16 control deceased. RESULTS: The brown staining on the cell membrane of myocardium showed positive result. There was a prominent CAR expression in VMC group and DCM group, which were statistically significant difference compared with control group (P < 0.05). CONCLUSION The CAR expression showed significantly higher in VMC and DCM groups. The viral infection can result in myocardial necrosis and impaired cardiac functions. These abnormalities can trigger a cascade of events that contributed to the progress of VMC to DCM.
Cardiomyopathy, Dilated/pathology* ; Case-Control Studies ; Coxsackie and Adenovirus Receptor-Like Membrane Protein ; Coxsackievirus Infections/complications* ; Death, Sudden, Cardiac ; Female ; Forensic Pathology ; Humans ; Immunohistochemistry ; Male ; Myocarditis/virology* ; Myocardium/pathology* ; Receptors, Virus/metabolism* ; Staining and Labeling

OBJECTIVE: Astragaloside is a simple substance of saponin and the active constituent of astragali. It was reported that the astragaloside exerted therapeutical eff ect on viral myocarditis and dilated cardiomyopathy. The purpose of this study was to investigate the effect of astragaloside on TL1A expression in viral myocarditis. METHODS: A total of 100 BALB/c mice were randomly divided into 6 groups: the normal control group (group A, n=10), the high-dose control group (group B, n=10), the myocarditis control group (group C, n=20), the low-dose group (group D, n=20), the middle-dose group (group E, n=20) and the high-dose group (group F, n=20). Mice in group A and group B were injected intraperitoneally with 0.1 mL EMEM solution, while mice in group C, D, E and F were treated with 0.1 mL of 1×102 TCID50 CVB3 (diluted in EMEM). Then, mice in group A and group B were treated with carboxymethycellulose solution and 9% astragaloside for 1 week, respectively. At the same time, mice in group C, D, E and F were treated with sodium carboxymethycellulose solution, 1% [0.07 g/(kg.d)], 3% [0.2 g/(kg.d)] and 9%[0.6 g/(kg.d)] astragaloside for 1 week, respectively. After 14 days, the mice were sacrificed and their hearts were collected. The expression levels of TL1A mRNA and protein in the myocardium were examined by RT-PCR and immunohistochemistry, respectively. RESULTS: There was no death in the group A and B. The mortality in the group C, D, E and F was 45% (9/20), 30% (6/20), 25% (5/20) and 10% (2/20), respectively. Compared with the group C, the mortality in the group F was significantly decreased (P<0.05), but there no significant difference in mortality between the group C and the group D or E (P>0.05). There was no any pathological lesion in the group A and B. The TL1A mRNA and protein expression in the myocardium of mice in the group A and B was at low level, with no difference between them (P>0.05). Compared with the group A, the expression levels of TL1A mRNA and protein in the group C were markedly up-regulated (P<0.01), which was dramatically attenuated by the intervention of astragaloside at high dosage (the group F, P<0.01) but not at low (the group D) or middle-dosage (the group E) (P>0.05). CONCLUSION Astragaloside may play a pivotal role in protection of the heart injury in viral myocarditis by suppressing the expression of TL1A.
Acute Disease ; Animals ; Cardiomyopathy, Dilated ; drug therapy ; Coxsackievirus Infections ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Mice ; Mice, Inbred BALB C ; Myocarditis ; drug therapy ; virology ; Myocardium ; metabolism ; pathology ; RNA, Messenger ; Saponins ; pharmacology ; Tumor Necrosis Factor Ligand Superfamily Member 15 ; metabolism ; Up-Regulation