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)

Asymmetric dimethylarginine (ADMA) is synthesized during the methylation of protein arginine residues by protein arginine methyltransferases (PRMT) and is released during proteolysis. ADMA is a competitive inhibitor of nitric oxide synthase and may decrease NO availability. ADMA is eliminated by renal excretion or is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) to citruline and dimethylamine. Two other endogenous methylarginines are also synthesized by PRMT: N-monomethyl-L-arginine (L-NMMA) and symmetric dimethylarginine (SDMA). L-NMMA inhibits NO synthase but its concentrations in circulation are much lower than ADMA whereas SDMA is inactive. Plasma concentration of ADMA is markedly increased in patients with chronic renal failure and moderately increased in patients with many other diseases including hyperlipidemia, diabetes mellitus, arterial hypertension, hyperhomocysteinemia and heart failure. The increased concentration of ADMA is positively correlated with markers of atherosclerosis, such as carotid artery intima-media thickness and has a predictive value for acute cardiovascular events in prospective studies. Angiotensin-converting enzyme inhibitors, angiotensin AT1 receptor antagonists, vitamin E and, according to some studies, estrogens used in hormonal replacement therapy reduce plasma ADMA concentration, which may contribute to their beneficial effect on NO synthesis and endothelial function. However, in some states associated with excess of NO, such as septic shock or excitotoxic neuronal injury ADMA may be protective by limiting toxic effect of high concentrations of NO. This article reviews the effect of pharmacotherapy on ADMA metabolism and its possible clinical implications.
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PMID:Asymmetric dimethylarginine (ADMA) as a target for pharmacotherapy. 1670 18

There is accumulating evidence that reactive oxygen species (ROS) play major roles in the initiation and progression of cardiovascular dysfunction associated with diseases such as hyperlipidemia, diabetes mellitus, hypertension, ischemic heart disease, and chronic heart failure. ROS produced by migrating inflammatory cells as well as vascular cells (endothelial cells, vascular smooth muscle cells, and adventitial fibroblasts) have distinct functional effects on each cell type. These effects include cell growth, apoptosis, migration, inflammatory gene expression and matrix regulation. ROS, through regulating vascular cell function, can play a central role in normal vascular physiology, and contribute substantially to the development of cardiovascular diseases. Excessive production of ROS is an essential mechanism underlying the pathogenesis of endothelial dysfunction and cardiovascular disease. Stem cells hold great promise for tissue repair and regenerative medicine, and endothelial progenitor cells (EPC) play a significant role in neovascularization of ischemic tissue. Recent studies have shown that cardiovascular risk factors such as hypertension, hypercholesterolemia, diabetes and cigarette smoking are inversely correlated with EPC number and function. Understanding the mechanisms, that regulate EPC function may provide new insights into the pathogenesis of vasculogenesis and may promote development of specific therapies to prevent ROS production and ultimately correct EPC dysfunction. We have demonstrated the angiotensin II receptor blockers improve EPC dysfunction through antioxidative mechanisms. In the present review, we describe our current understanding of the contributions of oxidative stress to progenitor and stem cell dysfunction in cardiovascular disease and focus on the potential mechanisms that underlie oxidative stress-induced damage of progenitor and stem cells.
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PMID:Oxidative stress on progenitor and stem cells in cardiovascular diseases. 1672 44

Recent studies suggest that adipose tissue hormones ("adipokines") are involved in the pathogenesis of various complications of obesity, including hyperlipidemia, diabetes mellitus, arterial hypertension, atherosclerosis, and heart failure. Apelin and visfatin are two recently described adipokines, although they are also synthesized outside adipose tissue. Apelin exists in at least three forms, consisting of 13, 17, or 36 amino acids, all originating from a common 77-amino-acid precursor. In the cardiovascular system, apelin elicits endothelium-dependent, nitric oxide-mediated vasorelaxation and reduces arterial blood pressure. In addition, apelin demonstrates potent and long-lasting positive inotropic activity which is preserved even in injured myocardium and is not accompanied by myocardial hypertrophy. Apelin synthesis in adipocytes is stimulated by insulin, and plasma apelin level markedly increases in obesity associated with insulin resistance and hyperinsulinemia. In addition to regulating cardiovascular function, apelin inhibits water intake and vasopressin production. Visfatin, previously recognized as a pre-B cell colony-enhancing factor (PBEF), is abundantly expressed in visceral adipose tissue and is upregulated in some, but not all, animal models of obesity. Preliminary studies suggest that plasma visfatin concentration is also increased in humans with abdominal obesity and/or type 2 diabetes mellitus. Visfatin binds to the insulin receptor at a site distinct from insulin and exerts hypoglycemic effect by reducing glucose release from hepatocytes and stimulating glucose utilization in peripheral tissues. Thus, apelin and visfatin are unique among adipose tissue hormones in that they are upregulated in the obese state and both exert primarily beneficial effects.
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PMID:Apelin and visfatin: unique "beneficial" adipokines upregulated in obesity? 1694 Sep 39

The role that dietary factors play in preventing heart failure (HF) and in improving prognosis is increasingly recognized, indicating a need for well-grounded guidelines that can provide recommendations for daily nutrient intakes. At present, however, the state of dietary guidance is more satisfactory for persons at risk of HF (Stages A and B) than for those with a diagnosis of HF (Stages C and D). For individuals at risk of HF, a good starting point is provided by governmental and professional society guidance directed at dietary management of cardiovascular risk factors such as hypertension, hyperlipidemia, and obesity. These dietary recommendations are consonant with epidemiologic research suggesting that improving risk factor profiles likely will lower the risk of developing HF. For patients with diagnosed HF, however, little information is available to define optimal nutrient intakes and optimal food patterns. Dietary services have been shown useful in improving clinical outcomes, but nutritional management must be individualized to the patient's needs and must accommodate pharmacologic therapy, multiple co-morbidities, the possible need for nutritional supplements, repeated hospitalizations, salt and fluid retention, voluntary vs. involuntary weight loss, and other nutritional issues relevant to the aged population who comprise the majority of HF patients. Progress in the field will require well-designed clinical investigations addressing nutrient intake, nutrient metabolism, and nutritional status while mindful of the complex pathophysiology of HF.
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PMID:Dietary guidance in heart failure: a perspective on needs for prevention and management. 1681 72

In the case of non-ST-segment elevation acute coronary syndromes (NSTE-ACSs), the acute use of certain antiplatelet agents is complicated by concerns about perioperative bleeding risks in patients requiring coronary artery bypass grafting (CABG) during the index hospitalization. As a result, clinicians often withhold potentially useful agents, such as clopidogrel, before determining patients' coronary anatomy. An accurate predictive model could allow for a better balance of this safety concern with the demonstrated benefits of agents such as clopidogrel. To create an accurate decision-making tool that would assess, at hospital presentation, the need for CABG in patients with NSTE-ACSs, we studied 61,974 high-risk patients with NSTE-ACS admitted to 311 CABG-capable hospitals participating in Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) from 2001 to 2003. A total of 8,395 patients (14%) underwent CABG during their initial hospital stay. A multivariate model was developed and identified 13 presenting clinical characteristics significantly associated with the likelihood of CABG (previous CABG, male gender, previous heart failure, diabetes, hyperlipidemia, renal insufficiency, ST depression and transient ST elevation, age > or = 75 years, previous percutaneous coronary intervention, family history of coronary artery disease, hypertension, trends in CABG rates, and previous stroke). This model had only modest predictive accuracy and calibration (c-index = 0.67). In conclusion, although certain presenting clinical features are associated with an increased likelihood of CABG in patients with NSTE-ACSs during the index hospitalization, it remains difficult to reliably identify, before diagnostic angiography, those who will subsequently undergo surgical revascularization.
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PMID:Challenges in predicting the need for coronary artery bypass grafting at presentation in patients with non-ST-segment elevation acute coronary syndromes. 1692 49

Caloric restriction extends longevity and reduces the onset of chronic disease in many animal models. Recently, caloric restriction was shown in humans to be associated with lower blood pressure, decreased systemic inflammation, and improved cardiac diastolic parameters. However, the causation and mechanisms of caloric restriction were obscured by the varied diet composition of the participants. The Dahl salt-sensitive rat which develops gradual, hypertension-associated diastolic dysfunction was used in this study to assess the impact of caloric restriction upon decompensated pressure-overload hypertrophy. Male Dahl salt-sensitive rats were provided either a low-salt diet or a high-salt diet to initiate heart failure progression. A further subset of high-salt rats underwent 15% calorie restriction, with salt load held constant. Parameters measured included serial systolic blood pressure, body weight, and changes of left ventricular systolic and diastolic parameters and ventricular geometry by echocardiography. After 18 weeks, fasting glucose, blood lipids, heart weight, kidney weight, lung weight, plasma interleukin-6 and TNF-alpha, and cardiac lipid peroxidation were measured. Low-salt rats did not develop heart failure. While high-salt rats displayed features of decompensated pressure-overload hypertrophy, moderate calorie restriction remarkably reduced morbidity. Compared to the high-salt fed group, the high-salt, calorie-restricted group showed reduced blood pressure, delayed onset of cachexia, lower fasting hyperlipidemia, lower cardiac, renal and lung weight, less plasma IL-6 and TNF-alpha, less cardiac oxidative damage, and improved diastolic chamber function and cardiac index. Modest calorie restriction, independent of salt intake, reduced pathogenesis in this well described model of decompensated pressure-overload hypertrophy.
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PMID:Moderate calorie restriction improves cardiac remodeling and diastolic dysfunction in the Dahl-SS rat. 1693 90

Cardiovascular disease causes the deaths of up to 50% of renal transplant recipients who have a functioning graft. As in other states of chronic kidney disease, both overload cardiomyopathy (chronic heart failure and left ventricular hypertrophy) and ischemic heart disease are evident; age and gender are important risk factors for both of these disorders. Potentially treatable risk factors include smoking, hyperlipidemia, diabetes and hypertension for ischemic heart disease, and anemia, hypertension and diabetes for cardiomyopathy. Although definitive evidence on the effectiveness of interventions is lacking, it seems reasonable to treat renal transplant recipients as patients at the highest risk of cardiovascular disease. Aggressive targeting of lifestyle factors, blood pressure, cholesterol and sugar regulation is likely to have a major impact on patient and graft survival and should be initiated well before transplantation. Maintenance of hemoglobin with erythropoietic agents is controversial but might improve quality of life. Although immunosuppressive agents have distinct effects on cardiovascular risk factors, the impact on outcomes is impossible to predict on the basis of current data, and no firm recommendations can be made.
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PMID:Therapy insight: management of cardiovascular disease in the renal transplant recipient. 1694 Oct 44

The use of doping substances and methods is extensive not only among elite athletes, but also among amateur and recreational athletes. Many types of drugs are used by athletes to enhance performance, to reduce anxiety, to increase muscle mass, to reduce weight or to mask the use of other drugs during testing. However, the abuse of doping substances and methods has been associated with the occurrence of numerous health side-effects. The adverse effects depend on the type of the consumed drug, as well as the amount and duration of intake and the sensitivity of the body, since there is a large inter-individual variability in responses to a drug. Usually the doses used in sports are much higher than those used for therapeutic purposes and the use of several drugs in combination is frequent, leading to higher risk of side-effects. Among biomedical side-effects of doping, the cardiovascular ones are the most deleterious. Myocardial infarction, hyperlipidemia, hypertension, thrombosis, arrythmogenesis, heart failure and sudden cardiac death have been noted following drug abuse. This paper reviews the literature on the adverse cardiovascular effects after abuse of prohibited substances and methods in athletes, aiming to inform physicians, trainers and athletes and to discourage individuals from using drugs during sports.
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PMID:ESC study group of sports cardiology position paper on adverse cardiovascular effects of doping in athletes. 1700 Dec 6

Inflammatory response of the endothelium has been increasingly recognized in the aetiopathogenesis of sporadic dilated cardiomyopathy (DCM). It has been shown that up to 2/3 of patients with DCM have immunohistological evidence of enhanced activation of the endothelium. We present a case of a middle-aged patient with a history of hypertension and hyperlipidaemia who developed sudden significant left ventricular dysfunction following flu-like syndrome. Endomyocardial biopsy revealed no myocarditis, but immunohistological features of endothelial activation were present. Additionally, increasing titers of IgG antibodies against PvB19 were observed. During 18 months of standard heart failure treatment along with statin therapy, we observed a significant recovery of left ventricular systolic function, and in this way, reversible dilated cardiomyopathy.
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PMID:[Reversible dilated cardiomyopathy in a patient with acute, advanced heart failure and intense endothelial inflammatory reaction in endomyocardial biopsy--a case report]. 1708 45

Coronary artery disease (CAD) is the main cause of death in renal transplant recipients. The aim of the present study was to determine the frequency and risk factors of post-transplantation CAD and its influence on the long-term results of surgery, as well as to evaluate the efficiency of myocardial revascularization in patients with severe CAD. Analysis of the observation of 479 renal recipients (332 men and 147 women) aged 38.69 +/- 11.2 was performed. The mean follow-up period was 64.56 +/- 37.44 months. Sixty-eight patients had diabetes mellitus. CAD was diagnosed in 14.8% (71 out of 479) renal recipients; in 12.7% of patients it developed de novo and was revealed 32.4 +/- 18.6 months after the surgery. Ten-year survival of renal recipients with CAD was only 39%, while in the group of non-CAD patients it was 75% (p < 0.0001). Age more than 45, male gender, diabetes mellitus, hypercholesterolemia, infections, pre-existing left ventricular myocardial hypertrophy, and renal transplant dysfunction were defined as significant risk factors of CAD de novo. Multi-factor Cox model found only age more than 45 (p < 0.009), male gender (p < 0.00001), and hyperlipidemia (p < 0.0058) to be independent risk factors of CAD. Myocardial revascularization was performed in 29 patients with coronary lesions: 27 patients underwent percutaneous transluminal coronary angioplasty with stenting and 2 patients underwent coronary artery bypass grafting (5 and 52 months after renal transplantation). However, angioplasty had to be repeated in 6 out of 27 (22%) patients within 3 to 6 months. The average follow-up duration was 23 months (2 to 74 months) after revascularization. Prolonged effect (more than 12 months) was achieved in 17 out of 29 (58.6%) patients. None of the patients developed myocardial infarction after revascularization. Two patients died 28 and 35 months after angioplasty due to extracardial complications (hepatic cirrhosis and an oncological disease); one patient died 78 months after repeated revascularization from progressive cardiac insufficiency while receiving dialysis due to a relapse of renal transplant insufficiency. Thus, CAD develops in 14.8% of renal transplant recipients; in 12.7 of patients it develops de novo. There are conventional and nonconventional post-transplantation CAD risk factors, which include renal transplant dysfunction and post-transplantation infections. Association with myocardial hypertrophy, observed in a significant number of patients, is a feature of post-transplantation CAD. Coronary revascularization, angioplasty with stenting in particular, may be considered to be an effective method of CAD treatment in renal transplant recipients.
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PMID:[Coronary artery disease after renal transplantation: epidemiology, risk factors, and surgical approaches to treatment]. 1713 51


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