Dilated cardiomyopathy (DCM) is a significant contributor to heart failure and can lead to life-threatening cardiovascular events at any stage. RNA-binding motif protein 20 (RBM20) gene mutation is known to be one of the causes of DCM. This mutation exhibits familial aggregation and is associated with arrhythmias, increasing the risk of sudden and early death. This article delves into the characteristics of the RBM20 gene, highlighting its role in regulating alternative splicing of the TTN gene and calcium/calmodulin-dependent protein kinase type II gene. Furthermore, the article provides a summary of treatment options available for DCM caused by RBM20 gene mutations, aiming to enhance clinicians' understanding of the RBM20 gene and provide new ideas for precision medicine treatment.
Humans ; Alternative Splicing ; Cardiomyopathy, Dilated/metabolism* ; Heart Failure/metabolism* ; Mutation

OBJECTIVETo observe the possible correlation between expression of chromogranin A (CGA) and myocardial fibrosis and investigate the potential role of CGA in the development of myocardial fibrosis in patients with dilated cardiomyopathy (DCM).

METHODSSurgical myocardial specimen from 10 DCM patients underwent successful orthotopic cardiac transplantation, and 3 normal myocardial specimen from brain-dead organ donors were obtained. CGA-mRNA, COLI-mRNA, COLIII-mRNA and ADAMTS-1-mRNA were analyzed by real-time PCR. The location and expression of CGA were assessed by immunohistochemistry(INH)with anti-CGA antibody. The collagen specific picrosirius red staining was applied on transversal myocardial slides and the collagen volume fraction (CVF) was calculated. The correlation between CGA and CVF was analyzed.

RESULTSCytoplasmic expression of CGA assessed by INH showed large amount of strong positive granules densely arranged in the epicardial and endocardial myocardiocytes in DCM specimen while there was only few sparse granules in the normal myocardium (P < 0.05). CVF was significantly higher in DCM myocardial specimen than that in normal specimen (P < 0.001). CGA-mRNA was significantly correlated with COLI-mRNA (r = 0.729), COLIII-mRNA (r = 0.95) and ADAMTS-1-mRNA (r = 0.665, all P < 0.05). Moreover, collagen deposition location was almost identical with the strong positive expression location of CGA.

CONCLUSIONWe demonstrated for the first time that the deposition of CGA was related with the myocardial fibrosis in DCM heart, therefore, CGA might play an important role by influencing myocardial remodeling and fibrosis in DCM patients.

Adult ; Cardiomyopathy, Dilated ; metabolism ; pathology ; Chromogranin A ; biosynthesis ; Female ; Fibrosis ; Humans ; Male ; Middle Aged ; Myocardium ; pathology

Animals ; Cardiomyopathy, Dilated ; metabolism ; Connexin 43 ; metabolism ; Disease Models, Animal ; Hypericum ; Male ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar

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*

Cardiomyopathy, Dilated/metabolism* ; Humans ; Microfilament Proteins/metabolism* ; Models, Cardiovascular ; Mutation ; Myocytes, Cardiac ; Pluripotent Stem Cells/metabolism* ; Transcription Factors/metabolism* ; Troponin T/metabolism*

OBJECTIVETo investigate whether calcineurin (CaN) contribute to tumor necrosis factor alpha (TNF-alpha)-induced cardiomyocyte hypertrophy.

METHODSThe protein content was assayed with lowry's method. The cardiomyocytes volumes were measured by computer photograph analysis system. The protein synthesis was assayed with [3H]-leucine incorporation method. [Ca2+]i transient was measured by Till image system by cell-loading Fura-2/AM. The expression of CaN was determined by Western blot.

RESULTS(1) (CsA (0.2 micromol/L), a selective CaN inhibitor, significantly suppressed the increase of protein content, [3H]-leucine incorporation and cell size induced by TNF-alpha. (2) CsA (0.2 micromol/L) significantly suppressed the elevation of the amplitude of the spontaneous Ca2+ transients induced by TNF-alpha in cultured ventricular myocytes from the neonatal rat. (3) TNF-alpha significantly increased the expression of CaN.

CONCLUSIONCa(2+) -CaN signaling pathway are involved in cardiomyocyte hypertrophy induced by TNF-alpha in rats.

Animals ; Calcineurin ; metabolism ; Calcium Signaling ; Cardiomyopathy, Dilated ; metabolism ; pathology ; Cells, Cultured ; Female ; Male ; Myocytes, Cardiac ; drug effects ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; pharmacology

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 investigate Fas protein expression of the myocardium in dilated cardiomyopathy (DCM) and its relationship with occurrence of sudden death caused by DCM. METHODS: Nine autopsy cases of sudden death caused by DCM along with the heart samples were chosen from the archives in the Department of Forensic Medicine, Tongji Medical College, HUST from 1997 to 2007. Other 11 cases which died of violence and other diseases were selected as the control group. Expressions of myocardial Fas protein in the samples were quantitatively detected by immunohistochemistry and computerized imaging analysis. RESULTS: Myocardial Fas protein expression increased significantly in the DCM group. Positive color showed brown-yellow granulated or striped distribution in the longitudinal section of myocardial within the cell membrane and cytoplasm, and showed circular brown granules in the cross section of the cell membrane, while these changes were not observed in the control group though there was focal weak staining noted. Statistical significance was observed between the experimental and control groups (P = 0.002), but no statistical significance was found for the average optical density value between these two groups (P = 0.675). CONCLUSION The expression of Fas protein increased obviously in the DCM group. Such alteration in expression quantity and distribution of myocardial Fas protein may be related to arrhythmia and heart failure in the patients with DCM.
Adult ; Apoptosis ; Autopsy ; Cardiomyopathy, Dilated/pathology* ; Case-Control Studies ; Death, Sudden, Cardiac/pathology* ; Female ; Forensic Pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Myocardium/pathology* ; Young Adult ; fas Receptor/metabolism*

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

BACKGROUNDMutations in the lamin A/C gene (LMNA) may cause familial dilated cardiomyopathy (dilated cardiomyopathy) characterized by early onset atrio-ventricular block (A-V block) before the manifestation of dilated cardiomyopathy and high risk of sudden death due to ventricular arrhythmia, which is very similar to the phenotype of gap junction related heart disease. This study aimed to determine the expression and localization of connexins in neonatal myocytes transfected with wild-type (WT) or mutant LMNA to elucidate how these mutations cause heart diseases.

METHODSWe studied the connexin 43 (Cx43) and connexin 40 (Cx40) expression in cultured neonatal myocytes transfected with wild-type (WT) or mutant LMNA (Glu82Lys (E82K) and Arg644Cys (R644C)) using confocal imaging and Western blotting analysis.

RESULTSCx43 protein expression was reduced by 40% in cells transfected with LMNA E82K than that in cells transfected with WT LMNA cDNA. Confocal imaging showed that the Cx43 located inside the cells by LMNA E82K. By contrast, LMNA E82K mutation had no effect on expression and localization of Cx40. LMNA R644C transfection did not show any significant effects on gap junctions at all.

CONCLUSIONSOur findings suggest that LMNA E82K significantly reduced the Cx43 expression and altered its localization which may be one of the pathological mechanisms underlying LMNA-related heart disease.

Animals ; Atrioventricular Node ; pathology ; Blotting, Western ; Cardiomyopathy, Dilated ; metabolism ; pathology ; Cells, Cultured ; Connexin 43 ; metabolism ; Connexins ; metabolism ; Fluorescent Antibody Technique ; Gap Junctions ; metabolism ; Humans ; Lamin Type A ; genetics ; physiology ; Mutation ; Rats ; Transfection