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)

Heart failure (HF) is a complex pathophysiologic state in which delivery of blood and nutrients is inadequate for tissue requirements. HF almost always arises in patients with previous cardiovascular disease such as acute myocardial infarction, atherosclerosis, cardiomyopathy, myocarditis, congenital malformations, or valvular disease. Recently, substantial progress has been made to understand the etiology, pathogenesis, and mechanisms of HF. Several inter-related mechanisms such as oxidative stress, signal transduction, abnormalities in intracellular calcium handling, mitochondrial dysfunction and inherited mutations have been proposed as the triggers of HF.
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PMID:[Molecular bases of heart failure]. 1746 31

Cardiac mast cells proliferate in cardiovascular diseases. In myocardial ischemia, mast cell mediators contribute to coronary vasoconstriction, arrhythmias, leukocyte recruitment, and tissue injury and repair. Arrhythmic dysfunction, coronary vasoconstriction, and contractile failure are also characteristic of cardiac anaphylaxis. In coronary atherosclerosis, mast cell mediators facilitate cholesterol accumulation and plaque destabilization. In cardiac failure, mast cell chymase causes myocyte apoptosis and fibroblast proliferation, leading to ventricular dysfunction. Chymase and tryptase also contribute to fibrosis in cardiomyopathies and myocarditis. In addition, mast cell tumor necrosis factor-alpha promotes myocardial remodeling. Cardiac remodeling and hypertrophy in end-stage hypertension are also induced by mast cell mediators and proteases. We recently discovered that cardiac mast cells contain and release renin, which initiates local angiotensin formation. Angiotensin causes coronary vasoconstriction, arrhythmias, fibrosis, apoptosis, and endothelin release, all demonstrated mechanisms of mast-cell-associated cardiac disease. The effects of angiotensin are further amplified by the release of norepinephrine from cardiac sympathetic nerves. Our discovery of renin in cardiac mast cells and its release in pathophysiological conditions uncovers an important new pathway in the development of mast-cell-associated heart diseases. Several steps in this novel pathway may constitute future therapeutic targets.
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PMID:Renin: at the heart of the mast cell. 1749 56

Oxidative stress has been widely recognized to be involved in the pathogenesis of cardiopulmonary disorders. In ischemic heart diseases, it is involved not only in the development of atherosclerosis but also in ongoing ischemic injury, especially in the reperfusion process. Cardiomyopathy is another cardiac disorder in which oxidative stress is involved. In diabetic cardiomyopathy, homocysteine, a well-known source of oxidative stress, is believed to play major roles in its development. Thioredoxin (TRX) is a redox-acting protein ubiquitously present in the human body. It also is inducible by a wide variety of oxidative stresses. TRX is a multifunctional protein and has anti-inflammatory and antiapoptotic effects, as well as antioxidative effects. It is therefore feasible to think that TRX is a potential therapy for cardiac disease. Moreover, serum TRX is a well-recognized biomarker of various diseases involving oxidative stress, and this is also the case for cardiac disorders. Here we discuss how TRX is useful as a biomarker of and therapeutic agent for cardiopulmonary disorders, especially focusing on ischemic heart disease, myocarditis and oxygen sensing, and acute respiratory distress syndrome.
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PMID:From oxygen sensing to heart failure: role of thioredoxin. 1751 84

Molecular imaging of functional parameters such as apoptosis (programmed cell death) in vivo opens new possibilities in clinical diagnostic and scientific research. Especially in the case of cardiovascular diseases that are mainly responsible for both morbidity and mortality in Western industrial nations, innovative non-invasive examination strategies are necessary for early diagnosis of these diseases. Since apoptosis unlike necrosis is present even after minor alterations of the microenvironment of cells and has been shown to be involved in a large number of cardiovascular diseases, there are currently several experimental studies underway with the goal of imaging apoptosis in vivo. The review discusses the basics of apoptosis in myocardial infarction, myocarditis, atherosclerosis, restenosis after angioplasty and stent implantation, currently used imaging techniques, achieved results, and future possibilities for molecular imaging of apoptosis.
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PMID:[Molecular imaging of apoptosis in cardiovascular diseases]. 1759 87

Inflammation underlies the pathogenesis of many common cardiovascular diseases (CVD) such as myocardial infarction, atherosclerosis, myocarditis and dilated cardiomyopathy. Allergic disorders like allergic rhinitis and asthma, both chronic inflammatory conditions, have recently been linked to increased CVD and death. Studies have found that increased IgE levels, eosinophilia, positive skin-prick tests, self-reported asthma and enzymes that regulate leukotriene synthesis (5-lipoxygenase) predict a high risk for atherosclerosis, stroke and myocardial infarction. Mast cells (MCs), cells involved in the pathogenesis of allergy and asthma, are emerging as key players in the regulation of inflammation and fibrosis in the heart and vasculature. Our laboratory has found that MC numbers are increased in mice susceptible to developing chronic dilated cardiomyopathy. The fibrosis associated with chronic heart disease is increased by MC degranulation. MCs can also act as antigen-presenting cells increasing inflammation in the heart through Toll-like receptor-4 signaling and increased proinflammatory cytokine production. Similar inflammatory mechanisms are observed for myocarditis and atherosclerosis. Many of the drugs currently used to reduce heart disease act on mediators/ pathways downstream of MC degranulation. An improved understanding of the role of MCs in regulating inflammation and fibrosis will enable researchers and clinicians to better treat heart disease.
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PMID:Mast cells and inflammatory heart disease: potential drug targets. 1833 55

Throughout the last 2 decades, experimental evidence from in vitro studies and preclinical models of disease has demonstrated that reactive oxygen and nitrogen species, including the reactive oxidant peroxynitrite, are generated in parenchymal, endothelial, and infiltrating inflammatory cells during stroke, myocardial and other forms of reperfusion injury, myocardial hypertrophy and heart failure, cardiomyopathies, circulatory shock, cardiovascular aging, atherosclerosis and vascular remodeling after injury, diabetic complications, and neurodegenerative disorders. Peroxynitrite and other reactive species induce oxidative DNA damage and consequent activation of the nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP-1), the most abundant isoform of the PARP enzyme family. PARP overactivation depletes its substrate NAD(+), slowing the rate of glycolysis, electron transport, and ATP formation, eventually leading to functional impairment or death of cells, as well as up-regulation of various proinflammatory pathways. In related animal models of disease, peroxynitrite neutralization or pharmacological inhibition of PARP provides significant therapeutic benefits. Therefore, novel antioxidants and PARP inhibitors have entered clinical development for the experimental therapy of various cardiovascular and other diseases. This review focuses on the human data available on the pathophysiological relevance of the peroxynitrite-PARP pathway in a wide range of disparate diseases, ranging from myocardial ischemia/reperfusion injury, myocarditis, heart failure, circulatory shock, and diabetic complications to atherosclerosis, arthritis, colitis, and neurodegenerative disorders.
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PMID:Role of the peroxynitrite-poly(ADP-ribose) polymerase pathway in human disease. 1853 82

Intravenous immunoglobulin (IVIG) is efficient in various immune mediated conditions. Various cardiovascular diseases are mediated by inflammatory processes and autoimmune mechanisms. Therefore, it seems conceivable to employ IVIG as an immunomodulating therapy in such indications. In this paper we review the possible anti-inflammatory effects of IVIG transfusion, and discuss the possible clinical implications in cardiology. Besides the established use of IVIG in Kawasaki disease, IVIG may be beneficial in some cases of heart failure, dilated cardiomyopathy, myocarditis, pericardial diseases, neonatal lupus, in the prevention of cardiac rejection following transplantation, and in modulating atherosclerosis. IVIG has been proven to be ineffective in rheumatic fever. Although uncommon, complications may arise including myocardial infarction, renal failure and hyperviscosity. IVIG should be administered based on accepted modes of transfusion.
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PMID:Intravenous immunoglobulin - indications and mechanisms in cardiovascular diseases. 1855 60

Systemic lupus erythematosus (SLE) is a multisystem disorder with numerous potential adverse effects on the cardiovascular system. These complications likely develop in most patients with SLE at some time during the course of their disease, in part due to the decreased mortality associated with SLE as a result of modem medical management. Conduction disturbances have been reported in the literature to occur primarily from the progression of SLE and secondarily from pharmacotherapy used to treat SLE and may first be evident on the electrocardiogram in the emergency department (ED) setting. Electrocardiogram abnormalities such as borderline first-degree heart block may be clues to more significant cardiac disease brought upon by years of chronic inflammation, myocarditis, vasculitis, and fibrosis that are often the result of longstanding autoimmune disease. It is essential that patients with autoimmune disease be screened carefully in the ED setting for underlying myocardial disease, particularly given the increased potential for atherosclerosis, ischemia, arrhythmias, and myocardial conduction defects in these patients.
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PMID:Rapid progression of atrioventricular nodal blockade in a patient with systemic lupus erythematosus. 1892 71

Toll-like receptors (TLRs) are a family of pattern recognition receptors that serve as a key part of the innate immune system. TLRs play a role in coordinating the organism's first line of defence against invading microbes or tissue injury. TLR-mediated inflammation is an important pathogenic link between innate immunity and a diverse panel of clinical disorders. Among these processes are cardiovascular disorders such as atherosclerosis, heart failure, viral myocarditis or diabetic angiopathies. In the new area of TLRs, this has generated a lot of interest from pharmaceutical companies as well as the investment communities. The improved understanding of TLRs, their key ligands and signaling cascades brought a number of diagnostic methods and compounds into clinical development. The first potential applications for TLR compounds include therapies for cardiovascular disease. The idea of this article is to describe the molecular basis of TLR signaling and review corresponding new inventions relating to TLR system and drug targets in cardiovascular disease.
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PMID:Targeting the toll-system in cardiovascular sciences. 1907 67

Autoimmunity may evolve in predisposed individuals following an exogenous trigger. Autoimmunity is affected by genetic, immune, hormonal, and environmental factors. Immune mechanisms in heart diseases are complex and often not completely understood. Several cardiac disorders are believed to be mediated by an immune reaction. Both humoral and cellular immunity are associated with the development of myocarditis, dilated cardiomyopathy, heart failure, rheumatic fever, and atherosclerosis. Here the diagnostic criteria and autoimmune aspects of autoimmune-mediated cardiac disorders are reviewed. New diagnostic criteria for "autoimmune dilated cardiomyopathy" were recently suggested by the authors. They presume that establishing a dominant autoimmune etiology in some patients will have clinical significance because these patients will potentially gain the greatest benefit from immunosuppressive and immunomodulating treatments.
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PMID:Autoimmunity and heart diseases: pathogenesis and diagnostic criteria. 1933 34


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