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

Heart disease is a rare but important complication of polymyositis. Diagnosis of myocardial disease is usually based on non-specific clinical, electrocardiographic, and echocardiographic data. This paper reports a case of polymyositis with myocardial disease diagnosed by myocardial imaging with radiolabelled antibody to myosin, a specific marker of the necrotic myocardial fibre.
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PMID:New application of myocardial antimyosin scintigraphy: diagnosis of myocardial disease in polymyositis. 848 80

A leading cause of sudden death among young athletes is the autosomal dominant genetic heart disease, familial hypertrophic cardiomyopathy (FHC). Mutations in several contractile proteins, including cardiac myosin heavy chains, have been described in families with FHC, leading to the hypothesis that FHC is a disease of the sarcomere (17). To create an animal model for this disease, five lines of transgenic mice have been produced that express a mutant myosin heavy chain in their hearts. The hearts of these mice exhibit the histopathological features seen in patients and demonstrate enlarged left ventricles. Our analysis suggests that the mutant protein acts as a dominant negative, since it constitutes only 5-10% of the total myosin in the heart. In addition, while the transgene is expressed in all chambers of the heart, only the left ventricle demonstrates pathology and enlargement, suggesting that several prominent features of the disease represent secondary responses influenced by other factors, such as hemodynamics.
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PMID:A murine model for hypertrophic cardiomyopathy. 858 73

Immunologic similarities have been demonstrated between Coxsackievirus B3 (CVB3), group A streptococcal M protein, and cardiac myosin. Previous studies have also shown that T lymphocytes obtained from CVB3-infected mice expressing the H-2k MHC haplotype gave an immunodominant proliferative response to the NT4 peptide (GLKTENEGLKTENEGLKTE) of the streptococcal M5 protein. We now show that the NT4 peptide can induce inflammatory heart disease in MRL/++ (H-2k) mice and that induction of anergy to this peptide protects against CVB3-induced myocarditis. MRL/++ mice infected with CVB3 for 7 days or immunized twice at 7-day intervals with the streptococcal NT4 peptide in CFA developed myocarditis. Treatment of the immunized mice with either anti-CD4 or anti-IAk mAbs inhibited cardiac inflammation. Injection of MRL/++ mice with NT4 covalently coupled to syngeneic splenocytes tolerized the animals to this peptide as shown by reduction of the proliferative response. NT4-tolerized mice had significantly reduced myocarditis, although virus titers in the heart were elevated. A control peptide, VP1-10 from the CVB3 capsid protein VP1, did not protect the mice from CVB3-induced myocarditis. The results suggest that immunity to NT4 induced during CVB3 infections is important to the development of cardiac inflammation.
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PMID:Streptococcal M protein peptide with similarity to myosin induces CD4+ T cell-dependent myocarditis in MRL/++ mice and induces partial tolerance against coxsakieviral myocarditis. 861 82

Immunization with cardiac myosin induces T cell-mediated myocarditis in genetically predisposed mice and serves as a model for autoimmune heart disease. This study was undertaken to identify pathogenic epitopes on the myosin molecule. Our approach was based on the comparison of the pathogenicity between cardiac (alpha-)myosin and soleus muscle (beta-)myosin. We show that alpha-myosin is the immunodominant isoform and induces myocarditis at high severity and prevalence whereas beta-myosin induces little disease. Therefore the immunodominant epitopes of alpha-myosin must reside in regions of different amino acid sequence between alpha- and beta-myosin isoforms. Cardiac myosin peptides corresponding to these regions of difference were synthesized and tested for their ability to induce inflammatory heart disease. Three pathogenic peptides were identified. One peptide that is located in the head portion of the molecule induced severe myocarditis, whereas two others that reside in the rod portion possessed only minor pathogenicity. The identification of pathogenic epitopes on the cardiac myosin molecule will allow detailed studies on the recognition of this antigen by the immune system and might be used to downmodulate ongoing heart disease.
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PMID:Identification of cardiac myosin peptides capable of inducing autoimmune myocarditis in BALB/c mice. 862 95

Immunization with cardiac myosin causes T cell-mediated myocarditis in genetically predisposed mice and serves as a model for autoimmune heart disease. The normal heart is not susceptible to T cells autoreactive with cardiac myosin; therefore, we investigated the conditions that are required to facilitate recognition of the target tissue. A.SW mice were immunized with cardiac myosin on Days 0 and 7. Major histocompatibility antigen (MHC Ag) and intercellular adhesion molecule-1 (ICAM-1) expression in the heart tissue was investigated by immunohistochemical techniques shortly before disease onset (ie, on Day 9). At this time point, cardiac interstitial cells expressing class II but not class I MHC Ag were significantly increased. In addition, endothelial ICAM-1 expression was strongly up-regulated. Myofibers did not show expression of these markers, and T cells were virtually absent. Because lipopolysaccaride (LPS) induced a similar distribution of class II MHC Ag and ICAM-1 in the myocardial tissue and because these molecules could be crucial to disease onset, we determined whether treatment with this immunomodulator renders the heart susceptible to passively transferred myosin-reactive T cells. We found that concanavalin A-activated spleen cells from myosin-immunized donors induced myocarditis in LPS-primed recipients, whereas normal mice were resistant to the injection of such cells. Increased class II MHC Ag expression after LPS-treatment was mediated by TNF because LPS-primed mice genetically lacking the TNF receptor failed to increase class II MHC Ag expression in the heart tissue. In summary, these results suggest that in cardiac myosin-induced myocarditis, expression of interstitial class II MHC Ag and/or endothelial ICAM-1 is a prerequisite for target organ recognition by autoreactive T cells.
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PMID:Cardiac myosin-induced myocarditis: target recognition by autoreactive T cells requires prior activation of cardiac interstitial cells. 864 80

The function of apolipoprotein J (apoJ) is unknown, but it has been hypothesized to be cytoprotective. In the normal heart, abundant apoJ mRNA and protein are expressed in atrial myocytes; no expression is detected in ventricular myocytes. To provide clues about the role of apoJ in the heart, the response of apoJ to heart disease, including three models of myocarditis and two models of in vivo pressure overload hypertrophy, were examined. In the disease model studied extensively, myosin-induced myocarditis, in situ hybridization detected induction of apoJ mRNA in ventricular myocytes immediately before histological evidence of injury. ApoJ message in ventricular myocytes reached high levels as myocarditis became more severe. Evidence of early apoJ induction, before inflammation and injury, also occurred in viral myocarditis. ApoJ mRNA was not present in the inflammatory or interstitial cells during myocarditis. In areas of severe inflammation and myocardial fiber degeneration, apoJ showed a gradient of expression, with highest levels in myocytes immediately surrounding the lesion and diminishing with increasing distance. ApoJ protein also accumulated in myocytes at the interface between degenerated myocardial tissue and the surrounding cardiac tissue. During cardiac hypertrophy that occurred without associated inflammation or cell damage, ventricular apoJ mRNA was not detected. When ischemic damage accompanied hypertrophy, apoJ was induced in the ventricular myocytes near the lesion borders. The correlation of apoJ induction with ventricular tissue damage, but not hypertrophy, suggests that apoJ is a repair response protein. We propose that apoJ functions to limit tissue injury and/or promote tissue remodeling.
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PMID:Apolipoprotein J/clusterin induction in myocarditis: A localized response gene to myocardial injury. 866 82

Challenge of several murine strains with two highly myocarditic variants of coxsackievirus B3 (CVB3) induced acute and chronic myocarditis, detectable at 21 and 45 days post-inoculation (p.i.). In-situ hybridization of coronal heart sections showing chronic inflammation with a radiolabelled CVB3 probe detected viral genomic RNA at day 7 p.i. but rarely at 21 or 45 days p.i., suggesting few murine heart cells actively replicate virus during chronic myocardial inflammation. Data will be presented that favour an alternative hypothesis, i.e. autoimmune responses to shared epitopes among CVB3 proteins, cardiac myosin and myocardial cell surface proteins (molecular mimicry) can affect the severity of chronic inflammation. Mice inoculated with human cardiac myosin (HM) prior to a CVB3m challenge develop less myocarditis than mice inoculated with virus only, suggesting that antibodies stimulated by HM bind virus, reduce the virus burden and provide protection. Mice inoculated with HM only develop non-neutralizing antibodies against purified CVB3m particles. Several strains of mice inoculated with specific synthetic peptides of HM produce antibodies against CVB3m and/or develop cardiomyopathy. Thus antigen-challenged mice can produce antibodies which cross-react among CVB3m HM or cardiac cells to protect or exacerbate heart disease.
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PMID:Coxsackievirus-induced chronic myocarditis in murine models. 868 3

Cardiac myosin-induced myocarditis proved to be a valuable virus-free murine model with which to investigate autoimmunological mechanisms in inflammatory heart disease. The disease was shown to be T cell-mediated. In this contribution the functional role of CD4 and CD8 molecules and the conditions that are required to make the cardiac tissue susceptible to an autoimmune attack are discussed.
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PMID:Cellular immune mechanisms in myosin-induced myocarditis. 868 7

Ag-specific activation of T lymphocytes requires two signals, one by the TCR and a second by costimulatory molecules. In a CD4+ T helper cell-dependent experimental autoimmune myocarditis model, we provide genetic evidence that cardiac myosin-induced autoimmune myocarditis and the production of IgG auto-Abs is dependent on functional T cells and did not occur in mice lacking the tyrosine kinase p56lck or the tyrosine phosphatase CD45. By contrast, animals lacking the T cell-costimulatory molecule CD28 (CD28 -/-) developed autoimmune heart disease, although at significantly lower severity than in heterozygous littermates, and produced IgG auto-Abs depending on the concentration of the autoantigen administered. In addition, the isotypes of IgG auto-Abs specific for cardiac myosin differed between CD28 +/- and CD28 -/- mice. Whereas CD28 +/- mice predominantly produced Th2-mediated IgG1 auto-Abs, CD28 -/- mice produced predominantly IgG2a. These data suggest that CD28 costimulation plays a crucial role in induction and maintenance of autoimmune heart disease and that CD28 expression is required for predominant Th2-IgG1 responses in an autoimmune setting.
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PMID:Induction of autoimmunity in the absence of CD28 costimulation. 875 65

Mutations in several muscle structural proteins (the myosin heavy chain, alpha tropomyosin, cardiac troponin T and myosin binding protein C) result in a genetically dominant heart disease, hypertrophic cardiomyopathy. Biochemical data from studies of mutant myosin suggest a dominant-negative mechanism for inheritance of this disease. The most likely primary defect is sarcomere dysfunction, which is followed by the major clinical symptoms.
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PMID:Contractile protein mutations and heart disease. 879 11


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