Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic lupus erythematosus (SLE) is a connective tissue disease characterized by the formation of autoantibodies and immune complexes. The heart and lungs are among the organ systems commonly affected in SLE. Pericarditis, premature coronary atherosclerosis, pleuritis and pulmonary infections are the most prevalent cardiopulmonary manifestations. Other rare associations include myocarditis, coronary arteritis, acute lupus pneumonitis/pulmonary haemorrhage, acute reversible hypoxaemia and 'shrinking lung' syndrome. Current imaging modalities may provide earlier detection of subclinical disease, which may aid in preventing these potentially fatal complications. The response to treatment varies, depending on the presentation of disease. In this chapter we address the frequency, diagnosis and monitoring, and treatment regimens of cardiac and pulmonary involvement in patients with SLE.
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PMID:How to manage patients with cardiopulmonary disease? 1204 50

The functional role of tumor necrosis factor (TNF)-alpha in the heart has been extensively studied over the last 15 years. Collectively, these studies have demonstrated that TNF-alpha has both diverse and potentially conflicting roles in cardiac function and pathology. These include beneficial effects, such as cardioprotection against ischemia, myocarditis, and pressure overload, as well as potentially adverse effects, such as the development of atherosclerosis, reperfusion injury, hypertrophy, and heart failure. TNF-alpha antagonist therapy recently has been demonstrated to be clinically applicable in inflammatory conditions, and clinical trials are currently in progress in the use of these agents in cardiovascular diseases. The scope for clinical applications of anti-TNF-alpha therapy in cardiovascular diseases is potentially extensive. Hence, this review has been undertaken to evaluate the cardiovascular effects of this pleiotropic cytokine and to evaluate the potential of targeting this cytokine in cardiovascular therapeutics. An overview of the TNF-alpha peptide and its associated signaling are described. This is followed by a discussion of the known roles of TNF-alpha in cardiac physiology and in a diverse array of cardiac pathologies. Reference to experimental and clinical studies using anti-TNF-alpha therapies are described where applicable. The postulated role of TNF-alpha signaling concerning innate cardiac cellular processes that may have direct adaptive effects in the heart will be reviewed with respect to future research directions. Finally, the author postulates that attenuation of TNF-alpha biosynthesis in selected individuals will need to be tested if true benefits of this therapeutic approach are to be realized in the management of cardiovascular diseases.
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PMID:Tumor necrosis factor-alpha in cardiovascular biology and the potential role for anti-tumor necrosis factor-alpha therapy in heart disease. 1219 98

Among all the autopsies performed between 1995 and 2000 in our Department, 77 adult cases of sudden death were selected. Sex, age, place of death, circumstances of death, causes of death and heart weight were reported from these 77 post-mortem records. A complete forensic autopsy was performed in every case. Sudden death occurred more frequently in males at rest. Strenuous activity was rarely involved in sudden death and 72.7% of the cases died from cardiovascular disease, mainly coronary atherosclerosis. Non-cardiac causes were dominated by pulmonary and neurological diseases. Cardiomegaly was a frequent finding in cases who died from cardiac pathology. This study underlines the importance of complete medico-legal investigations in case of sudden death. Multiple heart samples are required in order to detect focal microscopic lesions, such as myocarditis and some forms of cardiomyopathy with minimal gross abnormalities. The post-mortem diagnosis of such cardiomyopathies is very important because the family of the deceased may undergo a possible screening. Toxicology is useful in the diagnosis of epileptic seizure and in identifying drugs like metamphetamine as a risk factor for some lethal cardiovascular pathologies such as aortic dissection. Molecular biology can also be helpful when limits of morphological diagnosis have been reached.
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PMID:Sudden adult death: a medico-legal series of 77 cases between 1995 and 2000. 1262 84

Transfected muscle can be used as a secreting tissue for therapeutic proteins. Skeletal muscle transfection is increased by suitable electric pulse application (electrotransfer). We and others had shown that electrotransfer of interleukin-10 encoding plasmid is an effective strategy in animal models of chronic diseases such as myocarditis, atherosclerosis, or rheumatoid arthritis. In the present work, we have studied murine interleukin-10 production and secretion after i.m. electrotransfer. In immunocompetent mice, serum and muscle mIL-10 levels were enhanced by electrotransfer. Serum mIL-10 concentration reached rapidly a peak level 2 days after electrotransfer. It then decreased to background at day 14. Muscle mIL-10 mRNA and protein remained more stable, being detectable up to 84 days after electrotransfer. A boost reinjection led to similar high level of circulating mIL-10. The fast decrease of serum mIL-10 was not observed in SCID mice.
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PMID:Interleukin-10 expression after intramuscular DNA electrotransfer: kinetic studies. 1243 85

Clinical trials have established bosentan, an orally active non-selective endothelin (ET) receptor antagonist, as a beneficial treatment in pulmonary hypertension. Trials have also shown short-term benefits of bosentan in systemic hypertension and congestive heart failure. However, bosentan also increased plasma levels of ET-1, probably by inhibiting the clearance of ET-1 by endothelin type B (ET(B)) receptors, and this may mean its effectiveness is reduced with long-term clinical use. Preliminary data suggests that selective endothelin type A (ET(A)) receptor antagonists (BQ-123, sitaxsentan) may be more beneficial than the non-selective ET receptor antagonists in heart failure, especially when the failure is associated with pulmonary hypertension. Experimental evidence in animal disease models suggests that non-selective ET or selective ET(A) receptor antagonism may have a role in the treatment of atherosclerosis, restenosis, myocarditis, shock and portal hypertension. In animal models of myocardial infarction and/or reperfusion injury, non-selective ET or selective ET(A) receptor antagonists have beneficial or detrimental effects depending on the conditions and agents used. Thus clinical trials of the non-selective ET or selective ET(A) receptor antagonists in these conditions are not presently warranted. Several selective endothelin-converting enzyme inhibitors have been synthesised recently, and these are only beginning to be tested in animal models of cardiovascular disease, and thus the clinical potential of these inhibitors is still to be defined.
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PMID:The therapeutic potential of endothelin-1 receptor antagonists and endothelin-converting enzyme inhibitors on the cardiovascular system. 1243 1

Mast cells, producing different cytokines, chemokines, proteases, vasoactive substances and other mediators, are multifunction cells which play an important role in physiological reactions, as well as in pathological situations. In the human heart mast cells have been identified at the site of sarcolemma, in perivascular tissue, tunica adventitia of vessels, and also in coronary atheroma. Heart mast cells have a number of immunological and functional features that make them distinct from other mast cells, the features are believed to be due to microenvironmental influences on phenotypic and cytochemical characteristics. Mast cells play complex and considerable role in development of different pathological processes in the heart. Surface receptors to lgE (Fc epsilon RI) and anaphylotoxine G5a determine their participation in development of systemic and cardiac anaphylactic reactions. Direct activation of heart mast cells by intravenously injected substances used in therapy and diagnostics can also result in development of anaphylactoid reactions. It was shown that quantity and density of mast cells is much higher in patients with atherosclerosis, myocarditis, ischemic and dilated cardiomyopathy, than in humans without any cardiac pathology. Thus, the data allow to suggest that heart mast cells play an important role in regulation of a functional state of the myocardium both under normal and pathological conditions.
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PMID:[Mast cells in normal and diseased heart]. 1289 13

NF-kappaB is a pleiotropic transcription factor implicated in the regulation of diverse biological phenomena, including apoptosis, cell survival, cell growth, cell division, innate immunity, cellular differentiation, and the cellular responses to stress, hypoxia, stretch and ischemia. In the heart, NF-kappaB has been shown to be activated in atherosclerosis, myocarditis, in association with angina, during transplant rejection, after ischemia/reperfusion, in congestive heart failure, dilated cardiomyopathy, after ischemic and pharmacological preconditioning, heat shock, burn trauma, and in hypertrophy of isolated cardiomyocytes. Regulation of NF-kappaB is complicated; in addition to being activated by canonical cytokine-mediated pathways, NF-kappaB is activated by many of the signal transduction cascades associated with the development of cardiac hypertrophy and response to oxidative stress. Many of these signaling cascades activate NF-kappaB by activating the IkappaB kinase (IKK) complex a major component of the canonical pathway. These signaling interactions occur largely via signaling crosstalk involving the mitogen-activated protein kinase/extracellular signalregulated kinase kinases (MEKKs) that are components of mitogen activated protein kinase (MAPK) signaling pathways. Additionally, there are other signaling factors that act more directly to activate NF-kappaB via IkappaB or by direct phosphorylation of NF-kappaB subunits. Finally, there are combinatorial interactions at the level of the promoter between NF-kappaB, its coactivators, and other transcription factors, several of which are activated by MAPK and cytokine signaling pathways. Thus, in addition to being a major mediator of cytokine effects in the heart, NF-kappaB is positioned as a signaling integrator. As such, NF-kappaB functions as a key regulator of cardiac gene expression programs downstream of multiple signal transduction cascades in a variety of physiological and pathophysiological states. We show that genetic blockade of NF-kappaB reduces infarct size in the murine heart after ischemia/reperfusion (I/R), implicating NF-kappaB as a major determinant of cell death after I/R. These results support the concept that NF-kappaB may be an important therapeutic target for specific cardiovascular diseases.
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PMID:NF-kappaB as an integrator of diverse signaling pathways: the heart of myocardial signaling? 1455 89

Most patients suffering from systemic lupus erythematosus develop secondary heart disease at some time during the course of the primary illness. The most common forms of this type of heart disease are acute fibrinous pericarditis and hypertension. By means of echocardiography, an increased incidence of pericardial effusion has been demonstrated. Although commonly noted at autopsy, myocarditis is often clinically silent. However, endomyocardial biopsy may confirm its presence during life. Libman-Sacks endocarditis, although encountered in 40 to 50% of hearts at autopsy, is rarely diagnosed during life. When significant valve dysfunction such as aortic insufficiency or mitral regurgitation develops during the course of systemic lupus erythematosus, then Libman-Sacks endocarditis should be strongly suspected. Cardiac arrhythmias, first degree AV block, and acquired complete heart block may develop either de novo or in association with lupus pericarditis, myocarditis, vasculitis, etc. Complete congenital heart block has been reported in newborns of mothers with systemic lupus erythematosus, particularly those who have an antibody to a soluble tissue ribonucleoprotein antigen called RO(SS-A). Coronary arteritis and premature coronary atherosclerosis manifesting in either angina pectoris or myocardial infarction in young adults, particularly women suffering from systemic lupus erythematosus, have received attention recently. The development of hypertension and hyperlipidemia while such patients are receiving prolonged corticosteroid therapy has been incriminated as the significant risk factor in premature coronary atherosclerosis. Longstanding hypertension and congestive heart failure have unfavorable prognoses. This report is based on a cumulative review of 50 patients with acute and chronic systemic lupus erythematosus seen at our institution and in private practice during the last 10 years.
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PMID:Heart disease in systemic lupus erythematosus: diagnosis and management. 1522 37

The present paper proposes a new therapy using Trypanosoma cruzi trans-sialidase to treat diseases with unclear pathogenesis that present in common chronic inflammation and fibrosis. This hypothesis is based on recent findings that co-infection with mycoplasma and chlamydia is present in many of these diseases and that this enzyme was capable to eliminate or decrease the co-infection from the host. We identified that mycoplasmas and chlamydias are present in atherosclerosis, aortic valve stenosis, dilated cardiomyopathy, chronic chagasic myocarditis and cancer. We hypothetized that mycoplasmal infection may induce immunodepression in the host, favoring proliferation of pre-existent chlamydial infection and that elimination of mycoplasma would lead to improvement of the immune system resistance and the control of chlamydial proliferation. Mycoplasma has a particular parasitic relationship with host cells, involving strong adherence of their membranes, making it extremely difficult to eradicate mycoplasmal infection from the host. A new therapeutic approach is suggested using one or more agents that prevent or inhibit the adherence of mycoplasma to host cell membranes by removing sialic acid residues and preventing oxidation of the cells. The use of a neuraminidase enzyme, particularly the T. cruzi trans-sialidase enzyme, associated with treatment using anti-oxidating agents is proposed. Preliminary experimental animal and laboratory tests showed good results. The proposal that trans-sialidase from T. cruzi is efficient in combating co-infection of mycoplasma and chlamydia is based, at least in part, on the observation that chagasic patients suffering from T. cruzi infection present less mycoplasma and chlamydia infection in their tissues. Also, a lower incidence of the diseases above described to be related to mycoplasma infection is observed in chagasic patients. It is also hypothesized that co-infection with mycoplasma and chlamydia may induce oxidation of the host cells. Anti-oxidants such as those present in plant extracts may also be used in the treatment. Other diseases such as chronic hepatitis, glomerulonephritis, Multiple Sclerosis, Alzheimer's Syndrome and idiopathic encephalitis are other examples of chronic diseases where mycoplasma and chlamydia might be present, as they have the characteristics of unknown etiology, persistent chronic inflammation and fibrosis.
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PMID:Trypanosoma cruzi trans-sialidase as a new therapeutic tool in the treatment of chronic inflammatory diseases: possible action against mycoplasma and chlamydia. 1532 5

Connective tissue diseases (CTD) lead to a high prevalence of common cardiac manifestations (pericarditis and myocarditis) and of ischemic coronary events with a considerable increase in cardiac mortality related to premature atherosclerosis. Although there are several techniques able to detect cardiac involvement in CTD patients, the most useful and non-invasive technique is echocardiographic exam which is able to detect not only valvular abnormalities, pericardial diseases and pulmonary hypertension but also left ventricular (LV) systolic or diastolic (regional or global) wall motion dysfunction. It is also well known that transesophageal echocardiography (TEE) can better identify cardiac abnormalities, vegetations and embolic sources. Symptomatic patients with positive stress echocardiographic exam or dipyridamole thallium imaging test should be referred for possible cardiac catheterization, especially if a large ischemic territory is involved. Until now, the echocardiographic evaluation of coronary artery tree consisted of assessing regional and global left ventricular systolic and diastolic function at rest and during pharmacological stress test. Recently, a new echocardiographic noninvasive method that allows direct assessment of coronary flow velocity in the mid-distal portion of left anterior descending artery (LAD) has been developed and validated. Advanced ultrasound technology (high-frequency broadband transducer with second harmonic capability) has now made possible a direct arterial visualization and measurement of coronary artery flow in left anterior descending in CTD patients with the assessment of coronary flow reserve (CFR).
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PMID:The role of echocardiographic techniques in connective tissue diseases. 1582 3


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