UMLS:C0018801 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Questionnaires were sent to 46 hospitals of all over Japan in order to obtain the clinical data on sarcoidosis patients who were treated with oral corticosteroids. The number of female patients was greater than that of male patients (1.5:1), and the average age was 44.9 +/- 16.5 with peaks at 20 and at 50 to 60. The markers of disease activity were high in serum or bronchoalveolar lavage fluids (BALF): specifically, the serum angiotensin-converting enzyme (sACE) was 27.9 +/- 31.9 IU/ml (n.v. < 21.4), and the CD4/CD8 lymphocyte ratio was 6.5 +/- 5.7. Eye involvement was the most common reason for systemic steroid therapy, followed in order by lung and heart involvement. The main reasons for steroid therapy were the exacerbation of ocular symptoms, visual disturbance, respiratory symptoms, such as cough or exertional dyspnea, progression of chest radiographic findings, heart failure and severe arrhythmia, such as AV block. The initial corticosteroid dose was usually 30 mg of predinisolone per day, but for some refractory cases, a 40-60 mg per day was used. Immunosuppressive drugs, such as methotrexate, were also used in the small number of patients who responded poorly to the steroid. Overall, a good clinical response to the drug was found in 70-80% of the steroid treated patients, but in those with cardiac disease, the response rate was only 48%.
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PMID:Clinical characteristics of 195 Japanese sarcoidosis patients treated with oral corticosteroids. 1462 Jan 65

We evaluated the expression of chemokine receptors (CCR1, CCR2, CCR5, and CXCR4) on the surface of peripheral blood mononuclear cells obtained from patients with chronic chagasic cardiomyopathy (CCC) and noninfected individuals. Only CCR5 and CXCR4 expression was different on the surface of the subsets (CD4, CD8, and CD14) evaluated. Patients with mild CCC had elevated leukocyte expression of CCR5, compared with noninfected individuals or those with severe disease. CXCR4 expression was lower on leukocytes from patients with severe CCC. The differential expression of both receptors on leukocytes of patients with CCC was consistent and clearly correlated with the degree of heart function such that the lower the heart function, the lower the expression of either CCR5 or CXCR4. These results highlight the possible participation of the chemokine system in early forms of chagasic cardiomyopathy and the relevance of heart failure-induced remodeling in modifying immune parameters in infected individuals.
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PMID:Chemokine receptor expression on the surface of peripheral blood mononuclear cells in Chagas disease. 1472 85

In humans, spontaneous autoimmune attack against cardiomyocytes often leads to idiopathic dilated cardiomyopathy (IDCM) and life-threatening heart failure. HLA-DQ8 transgenic IAb knockout NOD mice (NOD.DQ8/Ab(0); DQA1*0301, DQB1*0302) develop spontaneous anticardiomyocyte autoimmunity with pathology very similar to human IDCM, but why the heart is targeted is unknown. In the present study, we first investigated whether NOD/Ab(0) mice transgenic for a different DQ allele, DQ6, (DQA1*0102, DQB1*0602) would also develop myocarditis. NOD.DQ6/Ab(0) animals showed no cardiac pathology, implying that DQ8 is specifically required for the myocarditis phenotype. To further characterize the cellular immune mechanisms, we established crosses of our NOD.DQ8/Ab(0) animals with Rag1 knockout (Rag1(0)), Ig H chain knockout (IgH(0)), and beta(2)-microglobulin knockout (beta(2)m(0)) lines. Adoptive transfer of purified CD4 T cells from NOD.DQ8/Ab(0) mice with complete heart block (an indication of advanced myocarditis) into younger NOD.DQ8/Ab(0) Rag1(0) animals induced cardiac pathology in all recipients, whereas adoptive transfer of purified CD8 T cells or B lymphocytes had no effect. Despite the absence of B lymphocytes, NOD.DQ8/Ab(0)IgH(0) animals still developed complete heart block, whereas NOD.DQ8/Ab(0)beta(2)m(0) mice (which lack CD8 T cells) failed to develop any cardiac pathology. CD8 T cells (and possibly NK cells) seem to be necessary to initiate disease, whereas once initiated, CD4 T cells alone can orchestrate the cardiac pathology, likely through their capacity to recruit and activate macrophages. Understanding the cellular immune mechanisms causing spontaneous myocarditis/IDCM in this relevant animal model will facilitate the development and testing of new therapies for this devastating disease.
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PMID:CD4 T cells play major effector role and CD8 T cells initiating role in spontaneous autoimmune myocarditis of HLA-DQ8 transgenic IAb knockout nonobese diabetic mice. 1675 19

The most common reason for heart failure in young adults is dilated cardiomyopathy often resulting from myocarditis. Clinical studies and animal models provide evidence that an autoimmune response against heart myosin is the underlying reason for the disease. IL-12 has been suggested to play a key role in development of experimental autoimmune myocarditis (EAM), as IL-12p40 and IL-12Rbeta1 knockouts are protected from disease. In this study, we have compared IL-12p40-/- mice, IL-12p35-/- mice and mice treated with a neutralizing IL-23 antibody in EAM and found that in fact IL-23, not IL-12, is responsible for inflammatory heart disease. However, these cytokines appear to have redundant activity for priming and expansion of autoreactive CD4 T cells, as specific T cell proliferation was only defective in the absence of both cytokines. IL-23 has been suggested to promote a pathogenic IL-17-producing T cell population. We targeted IL-17 by capitalizing on an active vaccination approach that effectively breaks B cell tolerance. Neutralization of IL-17 reduced myocarditis and heart autoantibody responses, suggesting that IL-17 is the critical effector cytokine responsible for EAM. Thus, targeting of IL-23 and IL-17 by passive and active vaccination strategies holds promise as a therapeutic approach to treat patients at risk for development of dilated cardiomyopathy.
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PMID:Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune myocarditis. 1707 13

Among the multiple cardiac manifestations occurring in HIV-infected patients, cardiomyopathy is one of the most challenging. Its incidence has only slightly decreased since the introduction of highly active antiretroviral therapy (HAART). Also, its pathogenesis remains relatively unclear. Although several studies demonstrated the presence of HIV genome in the heart of patients, more recent developments found that viral infection plays an indirect role only, as well as they recognized the contribution of proinflammatory cytokines in the progression of the disease. Experimental studies on animals and cultured myocytes have established the signalling pathway triggered by proinflammatory cytokines in heart failure and cardiomyopathy. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and IL-6 promote expression of inducible nitric oxide synthase (iNOS) in cardiomyocytes through activation of p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappaB (NFkappaB). TNF-alpha and high concentrations of NO also induce cardiomyocyte apoptosis by TNF type 1 receptor activation. This biological framework, which is also involved in progression of cardiomyopathy in humans, is more pronounced in HIV-infected patients, in whom proinflammatory cytokines TNF-alpha, IL-1 and IL-6 are increased, resulting in an enhanced expression of cardiac iNOS, especially in patients with a low CD4 T cell count. This may account for the worse outcome of heart failure in HIV-infected patients. However, there are only few data today to support future therapeutic implications of cytokines antagonism in treatment of HIV-infected patients with cardiomyopathy. Whether modulation of TNF production or selective inhibition of p38 MAPK pathway could be useful approaches remains uncertain.
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PMID:Cytokines in HIV-associated cardiomyopathy. 1733 7

The prevalence of inflammation is high among patients with chronic heart failure (CHF). Reduced ejection fraction was associated with frequency of CD4(+) T cells of leukocytes. Therefore, we investigated inflammatory cytokines of expression markers in CD4(+) T cells in patients with CHF. Blood samples were obtained from 103 patients with CHF, from 83 patients with stable angina (SA), and from 57 controls. Interferon-gamma (IFN-gamma)-positive CD4(+) T cells and interleukin-4 (IL-4)-positive CD4(+) T cells were analyzed using 3-color flow cytometry. The frequency (%) of IFN-gamma-positive CD4(+) T cells increased in patients with CHF compared with those with SA and controls (CHF: 28.3 +/- 13.8, SA: 23.50 +/- 10.38, controls: 19.00 +/- 7.45, P < 0.001). There was no significant difference in the frequency of IL-4-positive CD4(+) T cells among the three groups. The frequencies of CD4(+) T cells that stained for IFN-gamma decreased from 32.37% +/- 16.40% on admission to 26.91% +/- 12.53% after 2 weeks in 26 patients with CHF. B-type natriuretic peptide (pg/ml) and high-sensitivity C-reactive protein (mg/dl) levels decreased from 251.7 +/- 150.4 and 0.64 +/- 0.78 on admission to 208.2 +/- 166.4 and 0.36 +/- 0.34 after 2 weeks in the 26 patients with CHF. We have demonstrated expression of IFN-gamma production of CD4(+) T cells during CHF. Prevention of unwanted T cell activation could represent a new target in the treatment of CHF.
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PMID:Expression of interferon-gamma and interleukin-4 production in CD4+ T cells in patients with chronic heart failure. 1753 22

Chronic heart failure is associated with an activation of the immune system characterized among other factors by the cardiac synthesis and serum expression of proinflammatory cytokines. There is unequivocal clinical and experimental evidence that the cytokine tumor necrosis factor-alpha is involved in the development of chronic heart failure, but a putative cardiotoxic potential of the proinflammatory cytokine interferon (IFN)-gamma remains primarily unknown. To investigate this issue we analyzed the cardiac phenotype of SAP-IFN-gamma transgenic mice, which constitutively express IFN-gamma in their livers and hence exhibit high circulating serum levels of this cytokine. SAP-IFN-gamma mice spontaneously developed chronic active myocarditis, characterized by the infiltration of not only CD4(+) and CD8(+) T cells but also Mac2(+) (galectin 3(+)) macrophages and CD11c(+) dendritic cells, eventually culminating in cardiomyopathy. Echocardiographic analyses exhibited a left ventricular dilation and impaired systolic function induced by IFN-gamma overexpression. IFN-gamma-mediated cardiotoxicity was associated with high-level cardiac transcription of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-12 and the macrophage-attracting chemokines MCP1 and MIP1-alpha. Myotoxic IFN-gamma effects could not be detected in smooth or striated muscle tissue, suggesting cardiomyocellular specificity of the toxic IFN-gamma effect. The precise mechanism of IFN-gamma cardiotoxicity remains to be elucidated.
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PMID:Interferon-gamma induces chronic active myocarditis and cardiomyopathy in transgenic mice. 1755 94

The percentage of CD4(+) T cells in blood is correlated with left ventricular dysfunction and decreased ejection fraction in heart disease. The aim of this study was to determine the relation between activation of CD4(+) T cells and New York Heart Association functional classes in chronic heart failure (HF) and differences in inflammatory activation between ischemic cardiomyopathy (IC) and idiopathic dilated cardiomyopathy (IDC). Blood samples were obtained from 47 patients with HF and 20 controls. Percentages of interferon-gamma-positive CD4(+) T cells (representative type 1 T-helper cells) and interleukin-4-positive CD4(+) T cells (representative type 2 T-helper cells) were analyzed using 3-color flow cytometry. The proportion of interferon-gamma-positive CD4(+) T cells was higher in patients with HF (28.96 +/- 12.90%) than in controls (18.12 +/- 5.28, p = 0.0006), but there was no difference in percentage of interleukin-4-positive CD4(+) T cells between the 2 groups. The proportion of interferon-gamma-positive CD4(+) T cells and plasma B-type natriuretic peptide levels increased with worsening of New York Heart Association functional class in the IC and IDC groups. The proportion of interferon-gamma-positive CD4(+) T cells in the IC group (33.88 +/- 13.33%) was higher than in the IDC group (22.33 +/- 8.88%, p = 0.002); however, plasma B-type natriuretic peptide levels were higher in the IDC group (358.0 pg/ml, 327.5 to 1,325.7) than in the IC group (82.7 pg/ml, 34.7 to 252.9, p = 0.019). In conclusion, we demonstrated pronounced type 1 T-helper cell activation in patients with HF in proportion to severity of HF and that the specificity of T-cell activation differs between patients with IC and those with IDC.
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PMID:Relation between CD4+ T-cell activation and severity of chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. 1765 33

The concept of CCR5 antagonists introduces an additional molecular target. Maraviroc (MVR) is approved by the FDA for use in HIV-1 infected patients for combination antiretroviral treatment of adults infected with only CCR5-tropic HIV-1 who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents. Tropism and treatment history should guide the use of MVR. Data from clinical trials show significant efficacy of MVR for patients with pre-treatment and multiple class failure. Additional clinical data show a CD4 reconstitution that is more pronounced than with comparator in treatment naive and in late stage patients even without CCR5-tropic virus indicating patients in earlier stages and even patients without CCR5 testing will benefit from MVR. MVR is not licensed for treatment naive patients but it has a high potential for further development in this patient group. It shows better immunological reconstitution than efavirenz. Pooled safety data from all available trials shows good short term tolerability. Caution is needed in hepatitis co-infection with pre-existing liver damage and in patients with heart failure. Isolates from different geographic regions differ in coreceptor usage. Summarizing knowledge on HIV-1 subtypes and CCR5 tropism shows that in principle all subtypes are susceptible to MVR. However, in subtypes A and D dualtropic and alternative coreceptor use were found. Clinical efficacy in patients from regions with A and D predominance should be studied in future trials. In conclusion, MVR will be of benefit for patients in various treatment situations and regions.
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PMID:Treatment with CCR5 antagonists: which patient may have a benefit? 1793 26

The aim of the investigation was to study a possibility to improve left ventricular (LV) volume and function remodelling in patients with chronic cardiac insufficiency (CCI) by means oftwo-stage bone marrow cell (BMC) activation: first in vivo and then ex vivo within the process of their cultivation. Two groups of CCI patients were recruited. Group 1 (controls) consisted of 50 patients undergoing conventional aorto-coronary bypass surgery (ACBS). Group 2 consisted of 57 patients injected with 200 million autological mononuclear BMC intramyocardially during ACBS. In Group 2 patients, the severity of immune dysregulation was assessed initially using blood leukocyte stimulation index (SI) values. Sixteen patients with SI >1 and moderate immunographic alterations were considered to have a favorable prognosis for BMC treatment; 41 subjects with SI <1 and pronounced immunographic abnormalities were regarded as having an unfavorable prognosis for BMC application. Twenty-two patients with SI <1 were administered a preliminary immunocorrective course (in vivo BMC activation). Mononuclear BMC obtained from 38 patients with SI >1 and 19 patients with SI <1 were cultured for 5 to 7 days (ex vivo BMC activation). Positive changes in BMC phenotypical pattern were observed only in patients with SI >1: CD3, CD4, CD8, CD25, and some other measurements increased. Significant positive effects on LV function parameters and Duke Activity Status Index (DASI) values were revealed in patients with SI >1 six months after BMC administration. In vivo immunocorrection in combination with subsequent ex vivo BMC activation (n=38) promoted significant improvements in LV volume characteristics 6 months after ACBS vs. the controls (ACBS without BMC, n=50). In conclusion, to make the administration of autological BMC in CCI patients effective, two-staged BMC activation should be performed: in vivo activation with immunocorrectors should be followed by ex vivo activation of cultured cells.
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PMID:[Improvement of myocardial remodelling and functioning in patients undergoing surgical treatment of chronic cardiac insufficiency by two-staged elevation of the immunoregulatory reserve of autological bone marrow cells and their intramyocardial application]. 1832 Jun 53

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