Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Formation of inflammatory lesions, one of the pathologic consequences of infection with Trypanosoma cruzi, involves intricate cell-cell interactions in which cell adhesion molecules (CAMs) are involved. Sera from 56 Chagas' disease patients grouped according to disease severity were studied for the presence of soluble intercellular adhesion molecule-1 (s-ICAM-1), soluble endothelial selectin (s-E-selectin), soluble vascular cell adhesion molecule-1 (s-VCAM-1), soluble platelet selectin (s-P-selectin), and s-CD44 were studied to determine if they could be used alone or in different combinations as markers for specific diagnostic procedures. Comparisons were made between congenitally, acutely, and chronically infected patients and aged-matched, noninfected individuals, as well as between patients with chronic Chagas' disease grouped according to the severity of their heart-related pathology. No differences in levels of s-CAMs were detected between sera from children with congenital T. cruzi infection and sera from noninfected infants born from chagasic mothers. In contrast, titers of s-ICAM-1, s-VCAM-1, s-selectin, and s-CD44 but not s-P-selectin were significantly increased in sera from patients during the acute phase of infection with T. cruzi. Titers of s-VCAM-1 and s-P-selectin were increased in chronically infected patients. A positive association with disease severity in sera from patients with chronic disease was observed for the levels of s-P-selectin. In contrast, we found no association between clinical symptoms and levels of s-VCAM-1. Patients with chronic disease with severe cardiopathy also showed diminished levels of s-CD44 in comparison with healthy controls or patients with mild disease. The results are discussed in the context of pathology of Chagas' disease.
 ...
PMID:Soluble cell adhesion molecules in human Chagas' disease: association with disease severity and stage of infection. 902 89

We have previously shown that titers of soluble platelet selectin (s-P-selectin) and soluble vascular cell adhesion molecule-1 (s-VCAM-1) were increased in sera of patients with chronic Trypanosoma cruzi infection. In this study, we analyzed the expression of CD49d-integrins, that bind to VCAM-1, and sialyl Lewis x (SLe(x)), which binds selectins, in peripheral blood lymphocytes of 27 patients with Chagas' disease at different levels of disease severity. Patients with a mild form of Chagas' disease showed a lower number of CD49d(+) cells, in comparison with those with severe chronic cardiopathy. Decreased levels of CD49d(+) cells were detected in CD3(-) cell populations. Conversely, SLe(x) expression was found to be decreased in patients with severe Chagas' disease. Levels of soluble platelet endothelial cell adhesion molecule-1 (s-PECAM-1) were significantly increased in the plasma of patients with severe Chagas' disease while unaltered levels of MCP-1 were recorded. These data show that VCAM-1 and P-Selectin ligands are differentially expressed during the chronic phase of the Trypanosoma cruzi infection. These findings also reinforce a role of the P-selectin/SLe(x) adhesion pathway rather than very late antigen-4 (VLA-4)/VCAM-1, in the pathogenesis of Chagas' disease.
 ...
PMID:alpha 4 Integrins and sialyl Lewis x modulation in chronic Chagas disease: further evidence of persistent immune activation. 1130 61

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.
 ...
PMID:Autoimmunity and molecular mimicry in the pathogenesis of post-streptococcal heart disease. 1270 52

The targeting and recruitment of inflammatory cells to vascular endothelium in ischaemic heart diseases is mediated by Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule (VCAM-1) and E-selectin and proinflammatory cytokines. Accumulation of mononuclear cells to the endothelium is one of the earliest events in the formation of an atherosclerotic lesion. The aim of this study was to estimate the serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), vascular adhesion molecule-1 (sVCAM-1), selectin E (sE-selectin) in patients with acute myocardial infarction (Group 1--n = 18 patients: 3 women and 15 men, mean age--60 years), unstable angina pectoris (Grupa 2--n = 31 patients: 8 women and 23 men, mean age--62 years and stable heart disease (Grupa 3--n = 25 patients: 14 women and 11 men, mean age--61 years. The control group (Group 4--n = 20) consist of twenty healthy patient without coronary risk factors. ELISA method was used to determine the concentration of adhesion molecules of acute inflammation parameters, and traditional risk factors with using standard methods. The serum levels of sICAM-1, sVCAM-1 were markedly elevated in patients with acute myocardial infarction, unstable angina pectoris and stable heart disease compared to control group (p < 0.001, p < 0.004, p < 0.0002 for sICAM-1, p < 0.007, p < 0.003, p < 0.004 for sVCAM-1). Serum concentration of sE-selectin in three groups was similar, we did not find statistically significant differences between them. Furthermore, serum concentrations of adhesion molecules correlated with serum concentrations of acute inflammation parameters and traditional coronary risk factor for example BMI, systolic and diastolic blood pressure and lipid concentration. Additional serum concentration of sICAM-1 was elevated in smoking patients compared to non-smokers. We conclude that evaluation of adhesion molecules (sICAM-1 and sVCAM-1 in patients with heart diseases can be unspecific markers of activity of inflammatory process in coronary vascular endothelium.
 ...
PMID:[Assessment of serum levels of adhesion molecules (sICAM-1, sVCAM-1, sE-selectin) in stable and unstable angina and acute myocardial infarction]. 1475 Apr 16

The conjugated equine estrogens-only arm of the Women's Health Initiative trial, showing a trend toward protection from heart disease as opposed to women receiving also medroxyprogesterone acetate (MPA), strengthens the debate on the cardiovascular effects of progestins. We compared the effects of progesterone (P) or MPA on the synthesis of nitric oxide and on the expression of leukocyte adhesion molecules, characterizing the signaling events recruited by these compounds. Although P significantly increases nitric oxide synthesis via transcriptional and nontranscriptional mechanisms, MPA is devoid of such effects. Moreover, when used together with physiological estradiol (E2) concentrations, P potentiates E2 effects, whereas MPA impairs E2 signaling. These findings are observed both in isolated human endothelial cells as well as in vivo, in ovariectomized rat aortas. A marked difference in the recruitment of MAPK and phosphatidylinositol-3 kinase explains the divergent effects of the two gestagens. In addition, both P and MPA decrease the adhesiveness of endothelial cells for leukocytes when given alone or with estrogen. MPA is more potent than P in inhibiting the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. However, when administered together with physiological amounts of glucocorticoids, MPA (which also binds glucocorticoid receptor) markedly interferes with the hydrocortisone-dependent stabilization of the transcription factor nuclear factor kappaB and with the expression of adhesion molecules, acting as a partial glucocorticoid receptor antagonist. Our findings show significant differences in the signal transduction pathways recruited by P and MPA in endothelial cells, which may have relevant clinical implications.
 ...
PMID:Differential signal transduction of progesterone and medroxyprogesterone acetate in human endothelial cells. 1535 73

Pulmonary hypertension (PH), a risk factor for mortality in sickle cell disease (SCD), has pathologic features of both pulmonary arterial hypertension (PAH) and PH related to left-sided heart disease (LHD) suggesting a link between these two entities. We hypothesized that both are characterized by endothelial dysfunction and increased adhesion molecule expression. SCD patients and normal volunteers underwent a screening questionnaire, echocardiogram, and blood donation for preparation of platelet-poor plasma. PAH was defined as a tricuspid regurgitant jet (TRJ) velocity > or =2.5 m/sec and/or the presence of isolated right ventricular hypertrophy or decreased systolic function. LHD was defined as either left-sided systolic/diastolic dysfunction or significant valvular disease. Plasma vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P- and E-selectin, nitric oxide (NO(x)), erythropoietin, and vascular endothelial growth factor (VEGF) levels were assayed by enzyme-linked immunoassay. Forty-three percent of sickle cell anemia (HbSS) and 28% of hemoglobin SC disease (HbSC) disease patients had PAH. Additionally, 10-15% of SCD patients had LHD. VCAM-1 levels were significantly increased in HbSS patients compared with HbSC patients and normal volunteers. VCAM-1 and P-selectin levels correlated positively with TRJ velocity in HbSS patients (r = 0.45, P = 0.03, r = 0.2, P = 0.05, respectively). ICAM-1, E-selectin, NO(x), erythropoietin, and VEGF levels were similar across subject groups. PH is common in SCD and, at times, due to LHD. Increased VCAM-1 and P-selectin expression was associated with TRJ elevation regardless of etiology suggesting a similar effect on endothelial gene expression and possibly providing a pathologic link between PAH and PH related to LHD in SCD.
 ...
PMID:Pulmonary arterial hypertension and left-sided heart disease in sickle cell disease: clinical characteristics and association with soluble adhesion molecule expression. 1838 29

Depression is recognized as a predictor of increased cardiac morbidity and mortality. In addition, depressed patients exhibit an increase in the serum markers of endothelial dysfunction and platelet activation involved in the cascade of events leading to atherosclerosis. The purpose of this study was to determine the early and late-onset expression of various vascular markers in a rodent model of depression. Male DBA (an inbred strain of mice)/2J mice were exposed to either 7 weeks of controlled living conditions or unpredictable chronic mild stress (UCMS), and subsequently given daily fluoxetine (10 mg/kg) or NaCl (9%) during the last 5 weeks of the experiment. Depressive-like behavior was evaluated by using motivational and self-care behavior, including the assessment of the animal's coat state and grooming behavior. Enzyme-linked immunoassay was used to quantify matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and plasminogen activator inhibitor-1 (PAI-1) expression either immediately after the end of the UCMS procedure (short term condition) or 10 months later (long-term condition). Results indicate that 1) UCMS procedure induces a short-term depressive-like behavior in mice, defined as coat state deterioration, an effect that is prevented by fluoxetine treatment; 2) UCMS procedure has no effect on the short-term expression of the studied markers; however, UCMS increases expression of plasminogen activator inhibitor-1 only in the long-term group; 3) fluoxetine treatment is unable to counteract this UCMS-induced change; 4) aging induces behavioral perturbation, defined as a decrease in grooming motivation, and an increase of all the vascular markers in both control and UCMS groups and 5) pretreatment with fluoxetine has no protective effects on aging-induced behavioral and vascular alterations. Thus, in this model of depression-like behavior, UCMS appears to induce late-onset physiological changes, which are consistent with human studies indicating that depression is a risk factor for the development of heart disease.
 ...
PMID:Early and late-onset effect of chronic stress on vascular function in mice: a possible model of the impact of depression on vascular disease in aging. 2142 42

Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. Since radiation also induces inflammation, a possible mechanism is a change in the adhesiveness of vascular endothelial cells, triggering pro-atherogenic accumulation of leukocytes. To investigate this mechanism at the cellular level, the effect of X rays on adhesiveness of cultured human aortic endothelial cells (HAECs) was determined. HAECs were grown as monolayers and exposed to 0 to 30 Gy X rays, followed by measurement of adhesiveness under physiological shear stress using a flow chamber adhesion assay. Twenty-four hours after irradiation, HAEC adhesiveness was increased, with a peak effect at 15 Gy. Radiation had no significant effect on surface expression of the endothelial adhesion molecules ICAM-1 and VCAM-1. Antibody blockade of the leukocyte integrin receptors for ICAM-1 and VCAM-1, however, abolished the radiation-induced adhesiveness. Since these leukocyte integrins can be activated by chemokines presented on the endothelial cell surface, the effect of pertussis toxin (PTX), an inhibitor of chemokine-mediated integrin activation, was tested. PTX specifically inhibited radiation-induced adhesiveness, with no significant effect on nonirradiated cells. Therefore, radiation induces increased adhesiveness of aortic endothelial cells through chemokine-dependent signaling from endothelial cells to leukocytes, even in the absence of increased expression of the adhesion molecules involved.
 ...
PMID:Ionizing radiation increases adhesiveness of human aortic endothelial cells via a chemokine-dependent mechanism. 2208 41