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

Despite exposure levels estimated to be equivalent to smoking only 0. 1-1.0 cigarettes per day, exposure to environmental tobacco smoke (ETS) is estimated to increase the risk of death from coronary heart disease (CHD) between 25 and 35% above the risk of nonexposed persons. This surprisingly large risk associated with a seemingly small exposure has raised doubts about the validity of attributing the increased CHD risk to ETS exposure. This paper reviews various biases that have been hypothesized to account for the increased CHD risk associated with ETS in the epidemiologic studies and characterizes the adverse effects of ETS on thrombosis, vascular endothelium, and exercise tolerance observed in experimental studies of humans and laboratory animals. None of the identified factors that has been proposed to introduce a spurious association between ETS and heart disease seem to invalidate the epidemiologic findings, either separately or in combination. In addition, experimental studies of ETS and heart disease demonstrate that acute exposure of humans and other species to ETS affects platelet function, vascular endothelium, and myocardial exercise tolerance at exposure concentrations widely prevalent in the workplace. Because exposure to ETS affects multiple physiologic pathways, it appears biologically plausible that ETS could cause the substantial increase in CHD risk that has been observed in epidemiologic studies.
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PMID:Why is environmental tobacco smoke more strongly associated with coronary heart disease than expected? A review of potential biases and experimental data. 1059 42

Infection with Trypanosoma cruzi causes a generalised vasculitis of several vascular beds. This vasculopathy is manifested by vasospasm, reduced blood flow, focal ischaemia, platelet thrombi, increased platelet aggregation and elevated plasma levels of thromboxane A(2) and endothelin-1. In the myocardium of infected mice, myonecrosis and a vasculitis of the aorta, coronary artery, smaller myocardial vessels and the endocardial endothelium are observed. Immunohistochemistry studies employing anti-endothelin-1 antibody revealed increased expression of endothelin-1, most intense in the endocardial and vascular endothelium. Elevated levels of mRNA for prepro endothelin-1, endothelin converting enzyme and endothelin-1 were observed in the infected myocardium. When T. cruzi-infected mice were treated with phosphoramidon, an inhibitor of endothelin converting enzyme, there was a decrease in heart size and severity of pathology. Mitogen-activated protein kinases and the transcription factor activator-protein-1 regulate the expression of endothelin-1. Therefore, we examined the activation of mitogen-activated protein kinases in the myocardium by T. cruzi. Western blot demonstrated an extracellular signal regulated kinase. In addition, the activator-protein-1 DNA binding activity, as determined by electrophoretic mobility shift assay, was increased. Increased expression of cyclins A and cyclin D1 was observed in the myocardium, and immunohistochemistry studies revealed that interstitial cells and vascular and endocardial endothelial cells stained intensely with antibodies to these cyclins. These data demonstrate that T. cruzi infection of the myocardium activates extracellular signal regulated kinase, activator-protein-1, endothelin-1, and cyclins. The activation of these pathways is likely to contribute to the pathogenesis of chagasic heart disease. These experimental observations suggest that the vasculature plays a role in the pathogenesis of chagasic cardiomyopathy. Additionally, the identification of these pathways provides possible targets for therapeutic interventions to ameliorate or prevent the development of cardiomyopathy during T. cruzi infection.
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PMID:The role of endothelin in the pathogenesis of Chagas' disease. 1133 35

Coronary heart disease (CHD) has been and remains a major contributor to morbidity and mortality in developed countries. The most common form of CHD in the western world is atherosclerosis (AS), especially of the major coronary arteries. Failure to maintain an intact endothelium, as a result of episodic and/or persistent injury and perturbation of the vascular endothelium, promotes formation of fatty streaks which are considered initiation events of AS. Cellular constituents contributing to endothelial injury include endothelial cells, monocytes, platelets, and smooth muscle cells. Individuals diagnosed with AS face complex, enduring clinical complications and enormous medical costs. Simple and easily compliant prevention and treatment measures are therefore strategic considerations in the management of this vascular disease. Based on known risk factors for CHD, priorities in AS prevention should include smoking cessation, blood pressure control, and diet modification. In recent years, the possible benefits of low to moderate consumption of alcoholic beverages, particularly of red wine, in the prevention of heart disease has received increasing attention and debate in the popular media as well as in the scientific community. Such attention has been prompted by research findings supporting a relationship between red wine consumption and the French paradox. This phenomenon refers to people residing in certain parts of France where red wine is customarily consumed during meals having a low CHD mortality, despite living a lifestyle considered to have comparably high CHD risks, as those in the US and many other developed countries. Studies have reported that the cardioprotective effects of red wine are greater than those attributed solely to ethanol and other types of alcoholic beverages. The mechanism(s) underlying the greater CHD protective benefits of red wine have not been elucidated. Recently the polyphenol resveratrol (3,5,4'-trihydroxy-trans-stilbene), known to be abundantly present in red wine, compared to white wine, beer, or spirits, has been demonstrated to elicit a broad spectrum of biological responses in in vitro and in animal studies, including effects that are compatible with the cardioprotective roles proposed for red wine. These recently described effects of resveratrol will be reviewed in this article. We will first summarize published data showing an inverse association between consumption of alcoholic beverages/red wine and risk of CHD. A review of biosynthesis of resveratrol and its presence in food groups and wines will follow. Recent studies relating exposure to wine/resveratrol with reduction in myocardial damage during ischemia-reperfusion, modulation of vascular cell functions, inhibition of LDL oxidation, and suppression of platelet aggregation will be presented. The last section of this review will focus on a discussion of mechanism(s) by which resveratrol acts as a potential cardioprotective agent.
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PMID:Mechanism of cardioprotection by resveratrol, a phenolic antioxidant present in red wine (Review). 1140 43

Stroke is a leading cause of death and disability in the world, and the worldwide burden from stroke will increase further during the 21st century. Major advances in the treatment and prevention of stroke have occurred but additional measures are needed. Much of the modern care of stroke mimics the modern treatment of heart disease, in part because of the success of thrombolytic therapy in improving outcomes. Nevertheless, the impact of thrombolytic therapy is limited because of the short therapeutic window. Additional measures are needed to limit the neurological consequences of stroke. Prevention remains a critical component of the management of patients with cerebrovascular disease. Although surgical therapies and antithrombotic medications (antiplatelet agents and anticoagulants) are effective in lessening the likelihood of stroke or recurrent stroke, new strategies are needed to lower the risk further. Measures aimed at stabilizing the vascular endothelium or preventing fracture of atherosclerotic plaques show great promise. Medications including cholesterol-lowering agents and antihypertensive medications, such as the angiotensin-converting enzyme inhibitors, appear effective in stroke prevention. These agents could be combined with antithrombotic agents and surgical interventions to lessen the risk of stroke.
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PMID:Stroke: a vascular pathology with inadequate management. 1295 49

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.
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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

We have identified waved 3 (wa3), a novel recessive mutation that causes abnormalities of the heart and skin. The cardiac defect results in a severe and rapidly progressive dilated cardiomyopathy. We identified the gene mutated in these mice, which we call NFkB interacting protein1 (Nkip1), using positional cloning. Nkip1 is expressed in skin, heart and vascular endothelium and shares homology with a small family of proteins that play a role in the regulation of transcription factors. A C-terminal fragment of this protein was previously identified as the RelA associated inhibitor (RAI). We show that the full-length protein is larger than previously described, and we confirm that it interacts with NFkB in vivo. Expression analysis of genes known to be regulated by NFkB revealed that Intercellular adhesion molecule 1 (Icam1) expression is consistently elevated in mutant mice. This result suggests that wa3 mutant mice represent a potentially important model for the analysis of the role of inflammatory processes in heart disease.
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PMID:A mutation in NFkB interacting protein 1 results in cardiomyopathy and abnormal skin development in wa3 mice. 1566 56

Epidemiological evidence indicates that moderate alcohol consumption reduces the incidence of heart disease. Endothelial nitric oxide synthase (eNOS) is a key regulator of vascular homeostasis and myocardial functions through the controlled production of nitric oxide (*NO). These studies were conducted to determine if the apparent alcohol-associated cardioprotection is mediated, in part, through modulation of the eNOS protein and activity in the cardiovascular system. Rats were fed alcohol and eNOS protein and *NO production were evaluated at the end of 8 weeks. Myocardial and vascular function was assessed ex vivo in a subset of animals. Moderate alcohol improved postischemic myocardial systolic and diastolic function and attenuated the postischemic reduction in coronary vascular resistance. Moderate alcohol also enhanced maximum vascular relaxation by 26 +/- 0.2% and increased plasma *NO production concomitant with a greater than 2.5-fold increase in eNOS protein. Higher levels of alcohol impaired maximum vascular relaxation by 22 +/- 0.1%. These results suggest that moderate alcohol improves postischemic myocardial functions and increases *NO production by vascular endothelium. An increase in *NO may explain, at least in part, the cardioprotective benefits of moderate alcohol consumption.
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PMID:Evidence of cardiovascular protection by moderate alcohol: role of nitric oxide. 1604 25

The pathogenesis of coronary lesion development is a multi-factorial process involving a number of different cell types and covariates, and injury and dysfunction of the vascular endothelium is an important marker and likely participant in the initiation and/or progression of most forms of heart disease. In addition to chronic dysfunction of endothelial responses in patients with established heart disease, there is evidence that 'acute insults' can cause measurable dysfunction in vascular response in humans (drug toxicities, hypoxia, high fat meal). Such repeated acute insults may contribute to disease risk in otherwise healthy individuals or promote disease progression in established patients. Consumption of grape products, especially wine, has been linked to lower cardiovascular risk but the vascular endothelial effects of grape products in healthy normal subjects, in the absence of ethanol, have not been evaluated. We therefore tested the hypotheses that 1) a standardized product derived from fresh grapes (GP, acute and chronic consumption) improves endothelial performance in healthy normal young subjects, and 2) that concomitant grape consumption affects the 'acute endothelial insult' caused by a single standardized high fat meal (HF). Acute consumption of GP equivalent to 1.25 cups of fresh grapes caused significant improvement in brachial artery flow mediated dilation (FMD) within 3 h of consumption, when compared to control consumption of sugar solution (p<0.05). No acute changes in heart rate, hemodynamics, or lipid profiles were observed. When this 'dose' was then consumed twice daily for 3 weeks FMD was further improved and total antioxidant capacity in plasma was slightly increased (p<0.05), with no change in heart rate, hemodynamics, or lipid profiles. A single HF meal (900 cal, 49 g total fat) caused a 50% reduction in FMD response when consumed alone, and this effect coincided with increased blood triglyceride levels within 3 h post-consumption. In contrast the concomitant consumption of GP with the HF meal completely prevented this HF-induced vascular endothelial dysfunction (p<0.05), but had no effect on rising triglycerides. These data demonstrate that a modest intake of fresh grapes can have acute favorable effects on vascular endothelial function in normal healthy subjects, that chronic intake can further improve performance and concomitant intake can blunt the 'acute insult' to endothelium caused by a typical western HF meal. This effect is likely to be related to antioxidant effects at the endothelium, rather than changes in blood lipids. These data support epidemiological data of the health benefits of grapes, and demonstrate that 'favorable' food consumption can apparently reduce some toxicities induced by 'unfavorable' food consumption.
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PMID:Vasoprotective endothelial effects of a standardized grape product in humans. 1880 7

Atherosclerosis, the primary cause of heart disease and stroke is initiated in the vascular endothelium, and risk factors for its development include environmental exposure to persistent organic pollutants. Caveolae are membrane microdomains involved in regulation of many signaling pathways, and in particular in endothelial cells. We tested the hypothesis that intact caveolae are required for coplanar PCB77-induced up-regulation of monocyte chemoattractant protein-1 (MCP-1), an endothelium-derived chemokine that attracts monocytes into sub-endothelial space in early stages of the atherosclerosis development. Atherosclerosis-prone LDL-R(-/-) mice (control) or caveolin-1(-/-)/LDL-R(-/-) mice were treated with PCB77. PCB77 induced aortic mRNA expression and plasma protein levels of MCP-1 in control, but not caveolin-1(-/-)/LDL-R(-/-) mice. To study the mechanism of this effect, primary endothelial cells were used. PCB77 increased MCP-1 levels in endothelial cells in a time- and concentration-dependent manner. This effect was abolished by caveolin-1 silencing using siRNA. Also, MCP-1 up-regulation by PCB77 was prevented by inhibiting p38 and c-Jun N-terminal kinase (JNK), but not ERK1/2, suggesting regulatory functions via p38 and JNK MAPK pathways. Finally, pre-treatment of endothelial cells with the aryl hydrocarbon receptor (AhR) inhibitor alpha-naphthoflavone (alpha-NF) partially blocked MCP-1 up-regulation. Thus, our data demonstrate that coplanar PCB77 can induce MCP-1 expression by endothelial cells and that this effect is mediated by AhR, as well as p 38 and JNK MAPK pathways. Intact caveolae are required for these processes both in vivo and in vitro. This further supports a key role for caveolae in vascular inflammation induced by persistent organic pollutants.
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PMID:Up-regulation of endothelial monocyte chemoattractant protein-1 by coplanar PCB77 is caveolin-1-dependent. 1926 15

Although cardiac transplantation has become a viable therapeutic option for end-stage heart disease, long-term success is limited by rejection and medical complications of immunosuppression. Earliest events in rejection revolve around T-lymphocyte recognition of foreign antigen through a panel of specialized cell surface proteins. This is followed by a cascade of signaling events, transcription of multiple genes, and cytokine production. The central importance of these events, collectively known as T-cell activation, to the rejection process is underscored by the clinical utility of cyclosporine, which prevents T-cell activation. The specific site of action of cyclosporine within the T cell has recently been elucidated at the molecular level, revealing important details of T-cell biology. Once the immune response has been initiated, localization of inflammatory cells to the graft requires alteration in the functional state of the vascular endothelium, which can then express adhesive ligands for immune effector cells. Recent evidence suggests that host natural killer lymphocytes may play a role in this process. Understanding the molecular details of these and other early events in rejection will facilitate the development of more specific and effective immunosuppressive therapies.
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PMID:Initiation of cardiac allograft rejection New developments in cellular and molecular mechanisms. 2124 33


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