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

Available data suggest that hypertensive cardiopathy is principally determined by the phenoconversion that allows the myocyte to adapt to the new working conditions by re-expressing a fetal program. Nevertheless, in clinical conditions, the scheme is different. The above phenotype is modified by trophic factors, which originate from ischemia, senescence, diabetes, genetics, or neurohormonal reactions. This review only focuses on some of the most recent advances concerning the permanent changes in the myocyte. Changes in extracellular matrix have been excluded. Recently, emphasis has been on the kinetic basis of the myocardial dysfunction at the myosin level, the potential therapeutic utilization of transferring the adrenergic receptor gene, the participation of NO synthases in the adaptational process, the existence of an abnormal excitation-contraction coupling due to a redistribution of Ca2+ sparks, the role of the microtubule as a determinant of sarcomere motion, and the multifactorial origin of cell death by apoptosis.
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PMID:Biology of hypertensive cardiopathy. 1113 87

We tested the hypothesis that treatment of mdx mouse muscular dystrophy with the glucocorticoid deflazacort prevents cardiomyopathic lesions and is accompanied by changes in metabolism and gene expression that reflect the improved tissue integrity. Cardiac muscle pathology, expression of alpha-cardiac myosin heavy chain, DNA synthesis, laminin, and basic fibroblast growth factor (bFGF) were examined to characterize dystrophy and changes with treatment. The potential of proton magnetic resonance spectroscopy (H-NMRS) to track cardiac dystrophy and deflazacort effects was also studied. Deflazacort (but not equipotent prednisone) reproducibly decreased lesion prevalence and severity. Treatment also produced cardiomyocyte hypertrophy and a 5.4-fold increase in alpha-cardiac myosin content. Expression of bFGF messenger RNA (mRNA), notable around lesions, rose 3.3-fold, and laminin expression rose 2.1-fold after deflazacort. Studies using H-NMRS showed a cardiac "signature" with less glycine and taurine than limb muscle or diaphragm and shifts with progression of dystrophy (distinct from normal aging) in many metabolites. Increased taurine, acetate, and succinate were present after 2 weeks of deflazacort treatment but were not present after 4 weeks. Although paired kinetic and functional studies of myocardium will be needed to determine the origin of such changes, these results demonstrate the potential application of H-NMRS to monitor clinical heart disease and treatment. In addition, the metabolic effects of deflazacort were substantial in preventing the progression of cardiomyopathy in mdx mice and included increased expression of protectant and stabilizing factors and hypertrophy of cardiac myocytes.
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PMID:Metabolic shifts and myocyte hypertrophy in deflazacort treatment of mdx mouse cardiomyopathy. 1118 Feb 2

Rheumatic heart disease is an autoimmune sequela of group A streptococcal infection. Previous studies have established that streptococcal M protein is structurally and immunologically similar to cardiac myosin, a well-known mediator of inflammatory heart disease. In this study, we investigated the hypothesis that streptococcal M protein could produce inflammatory valvular heart lesions similar to those seen in rheumatic fever (RF). Fifty percent (3 of 6) of Lewis rats immunized with recombinant type 6 streptococcal M protein (rM6) developed valvulitis as well as focal lesions of myocarditis. Valvular lesions initiated at the valve surface endothelium spread into the valve. Anitschkow cells and verruca-like lesions were present. T cells from rM6-immunized rats proliferated in the presence of purified cardiac myosin, but not skeletal myosin. A T-cell line produced from rM6-treated rats proliferated in the presence of cardiac myosin and rM6 protein. The study demonstrates that the Lewis rat is a model of valvular heart disease and that streptococcal M protein can induce an autoimmune cell-mediated immune attack on the heart valve in an animal model. The data support the hypothesis that a bacterial antigen can break immune tolerance in vivo, an important concept in autoimmunity.
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PMID:Induction of autoimmune valvular heart disease by recombinant streptococcal m protein. 1134 78

The pathophysiology of viral myocarditis is still a matter of debate. Humoral autoimmunity in postviral heart disease remains an attractive but complex hypothesis. Antigenic mimicry with or without cytolytic antibody properties has been shown to play a role in the immunopathogenesis of myocarditis with respect to sarcolemmal/myolemmal epitopes (including the beta-receptor), myosin and some mitochondrial proteins including the antinucleotide translocator (ANT)-carrier and dihydrolipoamid dehydrogenase. Today, refined two-dimensional Western blots are able to identify receptors and enzymes that are target of a humoral immune response or the consequence of an "immunization process." A humoral immune response to an invading agent will most likely lead to immunodestruction first. After conversion to IgG, the continuing antibody response may indicate the healing or healed process and last for many years or life-long. This paper reviews our present knowledge on the humoral immune response in myocarditis and its interplay with the viral agents and the other components of the immune system.
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PMID:Pathophysiology of viral myocarditis: the role of humoral immune response. 1193 3

Molecular mimicry between pathogen and host has been proposed as a mechanism for the development of autoimmune diseases. Evidence suggests that microorganisms contain proteins which are similar enough to host proteins that they can stimulate existing B and T cells to respond to self proteins. The loss of immune regulation during responses against microbial antigens may explain development of pathogenic B and T cell responses in autoimmune diseases associated with infections. The study of B and T cell responses against the group A streptococcal antigens, N-acetyl-glucosamine, M protein and the autoantigen cardiac myosin has led to a better understanding of how molecular mimicry may play a role in disease. Studies of human monoclonal antibodies, T cell responses and animal models in comparison with the immunopathology in the human disease has provided information about the steps leading to inflammatory heart disease in autoimmune post-streptococcal rheumatic carditis. The new data indicate that the steps in pathogenesis of rheumatic heart disease following group A streptococcal infection include the following events. First, the development of crossreactive autoantibodies against the group A streptococcal carbohydrate antigen N-acetyl-glucosamine and cardiac myosin. Second, these antibodies react with valvular endothelium which becomes inflamed with expression of vascular cell adhesion molecule-1 (VCAM-1). After this event, T cells, CD4+ and CD8+, infiltrate through the endothelium/endocardium into the valve which is an avascular structure. Aschoff bodies or granulomatous lesions may form containing macrophages and T cells underneath the endocardium. The T cells are responsive to streptococcal M protein antigen sequences. The valve becomes scarred with eventual neovascularization and progressive, chronic disease in the valve. In the host, the mimicking antigens cardiac myosin and laminin have been involved in the myocardium and valve, respectively. As in other autoimmune diseases, both environmental and genetic factors are involved in the development of rheumatic carditis and inflammatory heart disease, a result of mimicry between the group A streptococcus and heart.
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PMID:Autoimmunity and molecular mimicry in the pathogenesis of post-streptococcal heart disease. 1270 52

Inflammatory heart diseases such as myocarditis and rheumatic heart disease result from the infiltration of the myocardium or valve with T cells and macrophages that result in scarring of the myocardium or valve and alteration in cardiac function. Our studies of T cells from these diseases have identified cardiac myosin in both rheumatic carditis and myocarditis as an important autoantigen. In rheumatic heart disease, streptococcal M protein specific T cells migrate to valves. By investigating streptococcal M protein and cardiac myosin in the Lewis rat model of myocarditis and valvulitis, T cell mimicry is supported as a potential mechanism in disease. Structural and immunological mimicry between the streptococcal M protein and cardiac myosin is shown directly in the Lewis rat model. Rat T cell lines demonstrate mimicry between cardiac myosin and M protein, and T cells isolated directly from inflammatory lesions in myocarditis respond to streptococcal M protein peptides. Studies in BALB/c mice also support the immunological crossreactivity of T cells primed against cardiac myosin with streptococcal M protein peptides containing cardiac myosin homologies. T cell lines produced from the Lewis rat specific to the cardiac myosin like sequences of streptococcal M protein migrated to the valves after passive transfer of the M protein specific T cell lines. In coxsackieviral myocarditis in the MRL mouse strain, cardiac myosin mimicking M protein peptide NT4 was found to induce tolerance and prevent coxsackieviral induced myocarditis, suggesting T cell mimicry between coxsackievirus and streptococcal M protein, both of which are associated with inflammatory heart disease. T cell mimicry between cardiac myosin and microbial antigens such as the streptococcal M protein may prime the immune system for inflammatory heart disease.
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PMID:T cell mimicry in inflammatory heart disease. 1503 18

The muscle protein myosin binding protein C (MyBPC) is a large multi-domain protein whose role in the sarcomere is complex and not yet fully understood. Mutations in MyBPC are strongly associated with the heart disease familial hypertrophic cardiomyopathy (FHC) and these experiments of nature have provided some insight into the intricate workings of this protein in the heart. While some regions of the MyBPC molecule have been assigned a function in the regulation of muscle contraction, the interaction of other regions with various parts of the myosin molecule and the sarcomeric proteins, actin and titin, remain obscure. In addition, several intra-domain interactions between adjacent MyBPC molecules have been identified. Although the basic structure of the molecule (a series of immunoglobulin and fibronectin domains) has been elucidated, the assembly of MyBPC in the sarcomere is a topic for debate. By analysing the MyBPC sequence with respect to FHC-causing mutations it is possible to identify individual residues or regions of each domain that may be important either for binding or regulation. This review looks at the current literature, in concert with alignments and the structural models of MyBPC, in an attempt to understand how FHC mutations may lead to the disease state.
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PMID:Myosin binding protein C: structural abnormalities in familial hypertrophic cardiomyopathy. 1511 10

Heart diseases are an important cause of morbidity and mortality in industrialized countries. Dilated cardiomyopathy (DCM), one of the most common heart diseases, may be the consequence of infection-associated myocardits. Coxsackievirus B3 (CVB3) can be frequently detected in the inflamed heart muscle. CVB3-induced acute myocarditis is most likely the consequence of direct virus-induced myocyte damage, whereas chronic CVB3 infection-associated heart disease is dominated by its immunopathological sequelae. Bona fide autoimmunity, for example, directed against cardiac myosin, may favor chronic destructive immune damage in the heart muscle and thereby promote the development of DCM. The immunopathogenesis of myocarditis and subsequent DCM induced either by pathogens or autoantigens can be investigated in well-established animal models. In this article, we review recent studies on the role of viruses, with particular emphasis on CVB3, and different immunological effector mechanisms in initiation and progression of myocarditis.
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PMID:Immunopathological basis of virus-induced myocarditis. 1515 5

Trypanosoma cruzi is the protozoan parasite that causes Chagas' heart disease, a potentially fatal cardiomyopathy prevalent in Central and South America. Infection with T. cruzi induces cardiac myosin autoimmunity in susceptible humans and mice, and this autoimmunity has been suggested to contribute to cardiac inflammation. To address how T. cruzi induces cardiac myosin autoimmunity, we investigated whether immunity to T. cruzi antigens could induce cardiac myosin-specific autoimmunity in the absence of live parasites. We immunized A/J mice with a T. cruzi Brazil-derived protein extract emulsified in complete Freund's adjuvant and found that these mice developed cardiac myosin-specific delayed-type hypersensitivity (DTH) and autoantibodies in the absence of detectable cardiac damage. The induction of autoimmunity was specific since immunization with extracts of the related protozoan parasite Leishmania amazonensis did not induce myosin autoimmunity. The immunogenetic makeup of the host was important for this response, since C57BL/6 mice did not develop cardiac myosin DTH upon immunization with T. cruzi extract. Perhaps more interesting, mice immunized with cardiac myosin developed T. cruzi-specific DTH and antibodies. This DTH was also antigen specific, since immunization with skeletal myosin and myoglobin did not induce T. cruzi-specific immunity. These results suggest that immunization with cardiac myosin or T. cruzi antigen can induce specific, bidirectionally cross-reactive immune responses in the absence of detectable cardiac damage.
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PMID:A cardiac myosin-specific autoimmune response is induced by immunization with Trypanosoma cruzi proteins. 1515 47

Four isoforms of cardiac troponin T (cTnT), a protein essential for calcium-dependent myocardial force development, are expressed in the human; they differ in charge and length. Their expression is regulated developmentally and is affected by disease states. Human cTnT (hcTnT) isoform effects have been examined in reconstituted myofilaments. In this study, we evaluated the modulatory effects of overexpressing one cTnT isoform on in vitro and in vivo myocardial function. A hcTnT isoform, hcTnT(1), expressed during development and in heart disease but not in the normal adult heart, was expressed in transgenic (TG) mice (1-30% of total cTnT). Maximal active tension measured in skinned myocardium decreased as a function of relative hcTnT(1) expression. The pCa at half-maximal force development, Hill coefficient, and rate of redevelopment of force did not change significantly with hcTnT(1) expression. In vivo maximum rates of rise and fall of left ventricular pressure decreased, and the half-time of isovolumic relaxation increased, with hcTnT(1) expression. Substituting total cTnT charge for hcTnT(1) expression resulted in similar conclusions. Morphometric analysis and electron microscopy revealed no differences between wild-type (non-TG) and TG myocardium. No differences in isoform expression of tropomyosin, myosin heavy chain, essential and regulatory myosin light chains (MLC), TnI, or in posttranslational modifications of mouse cTnT, cTnI, or regulatory MLC were observed. These results support the hypothesis that cTnT isoform amino-terminal differences affect myofilament function and suggest that hcTnT(1) expression levels present during human development and in human heart disease can affect in vivo ventricular function.
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PMID:cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform. 1551 65


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