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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Giant cell myocarditis is a serious and frequently fatal inflammatory heart disease of which the etiology remains unknown. In the present study, we investigated the origin of multinucleated giant cells in myocarditis with the use of an experimental model. We also examined the factors relating to the formation of giant cells in myocarditis. Severe myocarditis characterized by the appearance of multinucleated giant cells was induced in Lewis rats by immunization with cardiac myosin in complete Freund's adjuvant. Two types of giant cells, foreign body giant cell-like and myocytelike, were observed in this myocarditis. Immunohistochemical studies revealed that both types of multinucleated giant cells were stained with OX42 and ED1 (macrophage markers) and were not stained with anti-desmin antibody and HHF35 (markers for muscle fibers). Therefore, it is likely that multinucleated giant cells in this myocarditis are derived from macrophages. During the course of the disease, the appearance of multinucleated giant cells was restricted to a period corresponding with the fulminant phase of inflammation. When the severity of the disease was modulated by immunization with various doses of the antigen, multinucleated giant cells appeared only in severe myocarditis after inoculation of a large dose of the antigen. Administration of immunoadjuvants also affected the formation of giant cells. Most of the rats injected with cardiac myosin in complete Freund's adjuvant developed giant cell myocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characteristics of giant cells and factors related to the formation of giant cells in myocarditis. 193 32

We studied the clinical and pathologic features of 17 cardiac rhabdomyomas from 13 males and four females whose ages ranged from birth to 9 yr (mean, 36 wk). Eleven were multiple, and tumors were found throughout the heart. Four patients had congenital heart disease, and three had tuberous sclerosis; of the ten sporadic cases, four were surgical resections. Three of the four patients with surgical resections survived postoperatively. Two patients presented with sudden cardiac death. Immunohistochemical stains on seven tumor revealed diffuse positivity for myoglobin, actin, desmin, and vimentin, with negative results for S-100 protein, similar to adjacent cardiac muscle. We conclude that cardiac rhabdomyomas can be sporadic, can be associated with tuberous sclerosis, or can be seen with other cardiac malformations. They usually present early in life with a variety of symptoms, including sudden death, and attempts at resection may be successful.
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PMID:Cardiac rhabdomyoma: a clinicopathologic study. 202 Jun 64

Using an immunohistochemical technique, the development of the cytoskeletal proteins desmin, vimentin, and actin (using alpha isotype and non-isotype specific antibodies) was assessed using a semi-quantitative grading system in the pulmonary vascular smooth muscle of nine normal pigs and 19 normal humans at different ages, and in 13 children with pulmonary hypertensive congenital heart disease. In the normal of both species, immunostaining for vimentin decreased after birth and then increased gradually while immunostaining for desmin and alpha actin increased steadily with age. In pulmonary hypertension, immunostaining for alpha actin and vimentin showed an accelerated increase at between 2 and 8 months. Also, the media showed regional differences in immunostaining which preceded the development of intimal proliferation. The inner media showed less immunoreactivity for all cytoskeletal proteins studied than did the outer media. Within areas of intimal proliferation many cells were immunonegative. These results suggest that the cytoskeletal features of medial smooth muscle cells are remodelled in the normal infant; that this process is altered from at least 2 months in the pulmonary hypertensive infant; and that the smooth muscle cells immediately beneath the internal elastic lamina are remodelled before migrating to form intimal proliferation. Changes in cytoskeletal composition can be related to the previously described postnatal maturation of pulmonary vascular smooth muscle cells.
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PMID:Cytoskeletal features of immature pulmonary vascular smooth muscle cells: the influence of pulmonary hypertension on normal development. 276 90

The cardiac cytoskeleton and the extracellular matrix play an essential role for maintaining cellular integrity and function of the myocardium. The network of microtubules and intermediate filaments are disrupted by the inflammatory reaction which depends on resident cells (myocytes, fibroblasts, endothel cells) and on systemic cells (granulocytes, macrophages, monocytes, lymphocytes). Changes in the cardiac cytoskeleton and the extracellular matrix may affect contractile function, since the cytoskeleton organizes the intra- and intercellular architecture. The inflammation in heart disease and the induction of fibrosis are mediated by cytokines and growth factors derived from fibroblast activation and from the B- and T-cell activity. A possible connecting link for the induction of fibrosis is the presentation of the myocardial antigens to the immune system and its subsequent cellular and humoral autoreactive response (Figure 1). Different autoantibodies to sarcolemmal and myolemmal antigens, to laminin, to extracellular matrix proteins, to the collagens and to myofibrils were demonstrated both in endomyocardial biopsy and as circulating autoantibodies in the peripheral blood. The pathophysiological role of the cytoskeleton and the extracellular matrix are well defined for beta-tubulin, fibronectin, laminin, desmin, vimentin, vinculin and collagen: beta-tubulin is increased or altered in dilated cardiomyopathy (DCM). Fibronectin appears in irregular forms in DCM as well. Ultrastructural analysis showed an increased content of laminin in basement membranes. In addition anti-laminin antibodies were found in 73% of patients with myocarditis and in 78% of patients with DCM. Desmin (z-bands) are partly destroyed in DCM. Anti-desmin antibody titers as indicators of a possible secondary immune response are found high in patients with acute myocarditis declining during reconvalescence and are also elevated in DCM. The vimentin of the endothelial cells and the vinculin of the sarcolemmal membrane and the intercalated discs have been demonstrated to be irregularly shaped and increased in content in DCM whereas in myocarditis their appearance and content is still unknown. The intracellular content of collagen type 5 is increased in DCM and in myocarditis. The presence of autoantibodies to components of the cytoskeleton and the extracellular matrix in myocarditis and perimyocarditis is well-described. Antibodies to the myolemma and the sarcolemma are found in almost all patients with perimyocarditis in the serum or bound in the biopsy. Some of them have been known cytolytic in vitro to isolated heart cells. In pericarditis a shift to antibodies to the extracellular matrix, collagen and intermediate filaments is observed among the circulating antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[The extracellular matrix and cytoskeleton of the myocardium in cardiac inflammatory reaction]. 777 71

An inflammatory cardiomyopathy may develop in humans and experimental animals with chronic Trypanosoma cruzi infection (Chagas' disease). Among the possible mechanisms involved in the pathogenesis of Chagas' cardiomyopathy, induction of heart-specific autoimmune responses has recently received substantial experimental support. The goal of the current study was to determine whether cardiac Ag-specific antibodies are produced in T. cruzi-infected mice with heart disease and, if so, to determine their Ag specificities. Upon infection with the Brazil strain of T. cruzi, C57BL/6 mice develop a cardiomyopathy that is histologically similar to that observed in chronically infected humans. Antisera from these mice were found to react with three cardiac Ag, having relative molecular masses of 200, 150, and 53 kDa. p200 and p150 are specifically found in heart muscle, although p53 is found in skeletal muscle as well. C57BL/6 mice infected with the Guayas strain of T. cruzi, which do not develop cardiomyopathy, did not produce antibodies to p200, p150, or p53, indicating that these antibodies may be specific markers of cardiomyopathy. Finally, p200 and p53 were identified as the contractile protein myosin and the intermediate filament protein desmin, respectively. This last finding is of special interest, because antibodies specific for myosin or desmin have been detected in humans and experimental animals with other natural and experimental cardiomyopathies. This suggests that infection with particular strains of T. cruzi may lead to the development of a cardiac Ag-specific autoimmune disease, possibly involving one or more of the Ag identified in this study.
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PMID:Cardiac antigen-specific autoantibody production is associated with cardiomyopathy in Trypanosoma cruzi-infected mice. 830 Nov 48

The left ventricle (LV) plays a central role in the maintenance of health of children and adults due to its role as the major pump of the heart. In cases of LV dysfunction, a significant percentage of affected individuals develop signs and symptoms of congestive heart failure, leading to the need for therapeutic intervention. Therapy for these patients include anticongestive medications and, in some, placement of devices such as aortic balloon pump or left ventricular assist device, or cardiac transplantation. In the majority of patients the origin is unknown, leading to the term idiopathic dilated cardiomyopathy. During the past decade, the basis of LV dysfunction has begun to unravel. In approximately 30% to 40% of cases, the disorder is inherited; autosomal dominant inheritance is most common (although X-linked, autosomal recessive and mitochondrial inheritance occurs). In the remaining patients, the disorder is presumed to be acquired, with inflammatory heart disease playing an important role. In the case of familial dilated cardiomyopathy, the genetic basis is beginning to unfold. To date, 2 genes for X-linked familial dilated cardiomyopathy (dystrophin, G4.5) have been identified and 4 genes for the autosomal dominant form (actin, desmin, lamin A/C, delta-sarcoglycan) have been described. In 1 form of inflammatory heart disease, coxsackievirus myocarditis, inflammatory mediators, and dystrophin cleavage play a role in the development of LV dysfunction. This review describes the molecular genetics of LV dysfunction and provide evidence for a "final common pathway" responsible for the phenotype.
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PMID:Arrhythmogenic inherited heart muscle diseases in children. 1178 50

The left ventricle (LV) plays a central role in the maintenance of health of children and adults due to its role as the major pump of the heart. In cases of LV dysfunction, a significant percentage of affected individuals develop signs and symptoms of congestive heart failure (CHF), leading to the need for therapeutic intervention. Therapy for these patients include anticongestive medications and, in some, placement of devices such as aortic balloon pump or left ventricular assist device (LVAD), or cardiac transplantation. In the majority of patients the etiology is unknown, leading to the term idiopathic dilated cardiomyopathy (IDC). During the past decade, the basis of LV dysfunction has begun to unravel. In approximately 30-40% of cases, the disorder is inherited; autosomal dominant inheritance is most common (although X-linked, autosomal recessive and mitochondrial inheritance occurs). In the remaining patients, the disorder is presumed to be acquired, with inflammatory heart disease playing an important role. In the case of familial dilated cardiomyopathy (FDCM), the genetic basis is beginning to unfold. To date, two genes for X-linked FDCM (dystrophin, G4.5) have been identified and four genes for the autosomal dominant form (actin, desmin, lamin A/C, delta-sarcoglycan) have been described. In one form of inflammatory heart disease, coxsackievirus myocarditis, inflammatory mediators and dystrophin cleavage play a role in the development of LV dysfunction. In this review, we will describe the molecular genetics of LV dysfunction and provide evidence for a "final common pathway" responsible for the phenotype.
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PMID:Molecular genetics of left ventricular dysfunction. 1189 44

The Z-line is a multifunctional macromolecular complex that anchors sarcomeric actin filaments, mediates interactions with intermediate filaments and costameres, and recruits signaling molecules. Antiparallel alpha-actinin homodimers, present at Z-lines, cross-link overlapping actin filaments and also bind other cytoskeletal and signaling elements. Two LIM domain containing proteins, alpha-actinin associated LIM protein (ALP) and muscle LIM protein (MLP), interact with alpha-actinin, distribute in vivo to Z-lines or costameres, respectively, and, when absent, are associated with heart disease. Here we describe the behavior of ALP and MLP during myofibrillogenesis in cultured embryonic chick cardiomyocytes. As myofibrils develop, ALP and MLP are observed in distinct distribution patterns in the cell. ALP is coincident with alpha-actinin from the first stage of myofibrillogenesis and co-distributes with alpha-actinin to Z-lines and intercalated discs in mature myofibrils. Interestingly, we also demonstrate using ALP-GFP transfection experiments and an in vitro binding assay that the ALP-alpha-actinin binding interaction is not required to target ALP to the Z-line. In contrast, MLP localization is not co-incident with that of alpha-actinin until late stages of myofibrillogenesis; however, it is present in premyofibrils and nascent myofibrils prior to the incorporation of other costameric components such as vinculin, vimentin, or desmin. Our observations support the view that ALP function is required specifically at actin anchorage sites. The subcellular distribution pattern of MLP during myofibrillogenesis suggests that it functions during differentiation prior to the establishment of costameres.
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PMID:ALP and MLP distribution during myofibrillogenesis in cultured cardiomyocytes. 1258 84

One of the hallmarks of cardiomyopathy and heart failure is pronounced and progressive cardiomyocyte death. Understanding the mechanisms involved in cardiomyocyte cell death is a topic of great interest for treatment of cardiac disease. Mice null for desmin, the muscle-specific member of the intermediate filament gene family, develop cardiomyopathy characterized by extensive cardiomyocyte death, fibrosis, calcification, and eventual heart failure. The earliest ultrastructural defects are observed in mitochondria. In the present study, we have demonstrated that these mitochondrial abnormalities are the primary cause of the observed cardiomyopathy and that these defects can be ameliorated by overexpression of bcl-2 in desmin null heart. Overexpression of bcl-2 in the desmin null heart results in correction of mitochondrial defects, reduced occurrence of fibrotic lesions in the myocardium, prevention of cardiac hypertrophy, restoration of cardiomyocyte ultrastructure, and significant improvement of cardiac function. Furthermore, we have found that loss of desmin also diminishes the capacity of mitochondria to resist exposure to calcium, a defect that can be partially restored by bcl-2 overexpression. These results point to a unique function for desmin in protection of mitochondria from calcium exposure that can be partially rescued by overexpression of bcl-2. We show that bcl-2 cardiac overexpression has provided significant improvement of an inherited form of cardiomyopathy, revealing the potential for bcl-2, and perhaps other genes in the family, as therapeutic agents for heart disease of many types, including inherited forms.
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PMID:Bcl-2 overexpression corrects mitochondrial defects and ameliorates inherited desmin null cardiomyopathy. 1471 96

Right ventricular (RV) hypertrophy is an important problem in congenital heart disease. We determined the alterations in phenotype that occur in the initial phase of RV hypertrophy and their possible correlations with the degree of hypertrophy. Therefore, we performed a differential proteomic profiling study on RV hypertrophy using an animal model of pulmonary artery banding (PAB) in parallel with hemodynamic characterization. The RV homogenates were subfractionated in myofilament and cytoplasmic proteins, which subsequently were separated by two-dimensional gel electrophoresis (2-DE), excised, and analyzed by mass spectrometry (MS). The cytoplasmic fraction showed expression changes in metabolic proteins, indicative of a shift from fatty acid to glucose as a substrate for energy supply. Up-regulation of three HSP-27s (1.9-, 1.7-, and 3.5-fold) indicated an altered stress response in RV hypertrophy. Detailed analysis by immunoblotting and MS showed that two of these HSP-27s were at least phosphorylated on Ser15. The myofilament fraction showed up-regulation of desmin and alpha-B-crystallin (1.4-and 1.3-fold, respectively). This alteration in desmin was confirmed by 1-DE immunoblots. Certain differentially expressed proteins, such as HSP-27, showed a significant correlation with the RV weight to the body weight ratio in the PAB rats, suggesting an association with the degree of hypertrophy.
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PMID:Proteomic changes in the pressure overloaded right ventricle after 6 weeks in young rats: correlations with the degree of hypertrophy. 1591 12


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