Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leptin, the protein encoded by the obese gene, is a newly described hormone implicated in the regulation of energy balance. To examine the possible role of leptin in the energy dysregulation that frequently accompanies chronic heart failure, we examined plasma leptin concentrations and energy expenditure in 18 heart failure patients (aged 71 +/- 6 years) and 46 healthy elderly controls (66 +/- 6 years). Plasma leptin concentrations were measured by radioimmunoassay, daily energy expenditure by doubly labeled water, and body composition by dual-energy x-ray absorptiometry. Fat mass was lower (P < .01) in heart failure patients compared with healthy controls, whereas fat-free mass did not differ between groups. Plasma leptin concentrations were not different between heart failure patients and healthy controls (5.1 +/- 4.2 v 6.8 +/- 4.4 pg/mL) and remained similar after statistical control for fat mass (6.0 +/- 3.1 v 7.1 +/- 3.2 pg/mL). Plasma leptin was related to fat mass in heart failure patients (r = .92, P < .01) and healthy controls (r = .69, P < .01). Free-living daily and physical-activity energy expenditures were lower (P < .01) in heart failure patients compared with healthy controls. Plasma leptin concentrations were related to both daily (r = .67, P < .01) and resting (r = .67, P < .01) energy expenditure in heart failure patients, but not in healthy controls (r = .09 and r = .33, respectively). In conclusion, we found an association between plasma leptin concentrations and energy expenditure in heart failure patients, but not in healthy controls. Thus, leptin may participate in the regulation of energy expenditure and body energy stores in heart failure patients.
 ...
PMID:Plasma leptin concentrations and energy expenditure in heart failure patients. 910 53

Cachexia is a strong predictor for mortality in patients with congestive heart failure. To investigate the role of leptin and regulators of apoptosis in cardiac cachexia we compared leptin concentrations and their relation to the TNF system, interleukin 1-beta (IL-1b), and soluble Fas in patients with heart failure with and without cachexia. Patients with cardiac cachexia have increased levels of interleukin-1b compared to non-cachectic heart failure patients [mean(S.E.)=1.11(0.62) vs. 0.02(0.02), P=0.01] and decreased concentrations of leptin [10.79(3.93) vs. 23.24 (8.35), P=0.1]. Leptin levels correlate with TNF-RI in cachectic heart failure patients (r=0.58, P=0.018). The TNF-RI levels were also correlated with Fas, both in all the patients taken together (r=0.5, P=0.006) and in those with cachexia (r=0.52, P=0.036). Our data indicate that more prospective studies are needed to clarify the role of leptin in the pathophysiology of heart failure cachexia.
 ...
PMID:Leptin serum levels in cachectic heart failure patients. Relationship with tumor necrosis factor-alpha system. 1110 65

Long-lasting problem on the differentiation of adenohypophyseal cell, which prepares them for their specific tasks (somatotropic, lactotropic ect.), becomes elucidated after recognition of the differentiational effect of transcription factor Pit-1. Expression of that factor in somatotrops results in STH secretion, contrary to lactotrops producing prolactin. Subclinical hypothyreosis (increased TSH with normal T3 and T4) endangers vessel not because of hypercholesterolemia, but because of changes in the dynamics of the blood flow. The idea of cardiotropic effect of thyroidal hormones is supported by the finding that administration of trijodthyronine to children after the surgical correction of heart malformations (cardiopulmonary bypass) improves myocardial function--it elevates cardiac output and decreases requirements on the intensive care. Receptors for hormones in tissues are flexible, they can be "heterooligomers" for dopamine and somatostatin. Mutations of mineralocorticoid receptor may cause hypertension in pregnancy and progesterone receptors have several isoforms. Receptors can be also activated by short exposition to a hormone. Glucocorticoids have probably also membrane receptors. Diabetes mellitus "type I" needn't to be immunogenic and DM type II not only results from down-regulation of receptors and subsequent insulin resistance, but it can be also caused by defects in insulin secretion. Insulin has receptors in the brain and participates in the appetite regulation. The attempt to use "desensibilisation" by peroraly administered insulin in patients with immunogenic DM had no effect. Stress affects memory mechanisms, heavy emotional stress during gravidity can bring congenital malformations. The decrease of mental functions in aged women depends on the level of free estradiol (the fraction, which is not bound to plasma proteins). Activation of dopaminergic neurons can be achieved by neurotropic growth factors. Nesiritide is a recombinant brain natriuretic hormone successfully tested in heart failure. The role of leptin in the appetite regulation in man is still not clear, other signalling molecules may have also an effect, e.g., ghrelin, which primarily stimulates STH secretion and brings about weight gain. Sildenafil influences nitrergic neurons elsewhere than in penis, for example it has positive effects in patients with oesophageal achalasia.
 ...
PMID:[Endocrinology 1999-2000]. 1128 21

Patients with chronic heart failure (CHF) have metabolic abnormalities, leading to a catabolic syndrome, with progressive loss of skeletal muscle in advanced stages of the disease. Leptin, the product of an obesity gene, has been associated with energy expenditure and weight regulation. The aim of this study was to assess serum levels of leptin and its soluble receptor in relation to exercise intolerance and neurohumoral activation in patients with CHF. We investigated 53 patients with CHF left ventricular ejection fraction (LVEF) 25+/-1%, age 56.6+/-1.3 years, Maximal oxygen uptake (VO(2) max) 16.3+/-0.6 ml/min.kg) sub-classified according to peak oxygen consumption of > or <or=14 ml/min.kg and 11 age-matched controls (LVEF 70+/-1, age 60.5+/-4.0 years, (VO(2)max) 26.9+/-1.6 ml/min.kg). Body mass index-adjusted serum levels of leptin and soluble leptin receptor were increased in patients with CHF compared to the controls (0.28+/-0.03 vs. 0.22+/-0.04 ng.m(2)/ml.kg and 32.6+/-1.9 ng/ml vs. 22.9+/-2.3, P<0.05). This increase was even more pronounced in patients with CHF and severe exercise intolerance (0.43+/-0.08 vs. 0.21+/-0.02 and 0.22+/-0.04 ng.m(2)/ml.kg; P<0.01 vs. VO(2)max>14 ml/min.kg and controls). Elevated levels of leptin correlated with an increased serum concentration of TNFalpha (r=0.749, P<0.01) in this subgroup of patients with CHF. We conclude that patients with advanced CHF show elevated serum levels of leptin and its soluble receptor. This finding indicates that leptin may participate in the catabolic state leading to the development of cardiac cachexia in the course of CHF.
 ...
PMID:Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure. 1255 13

Results from animal experimentation suggest a 2-way interaction between leptin and the sympathetic nervous system, with leptin causing sympathetic activation and conversely, with the sympathetic system exercising regulatory feedback inhibition over leptin release. We have now tested this hypothesis in humans. In the absence of results from leptin infusions, to test for sympathetic stimulation of leptin release, we sought a quantitative naturalistic linkage of sympathetic activity with leptin plasma concentration across a broad range of leptin values in men of widely differing adiposity. Renal norepinephrine spillover was correlated with plasma leptin (r=0.628, P<0.01), but other measures of sympathoadrenal function did not. To test for sympathetic and adrenomedullary inhibition of leptin release, we studied clinical models of high sympathetic tone, heart failure, and essential hypertension, in which lowered plasma leptin levels might have been expected but were not found; a model of low sympathetic activity, pure autonomic failure, in which plasma leptin level was normal (6.1+/-1.2 vs 12.8+/-3.1 ng/mL in healthy subjects); and a clinical model of reduced epinephrine secretion, healthy aging, in which plasma leptin level again was normal (5.7+/-1.1 ng/mL vs 4.0+/-0.9 ng/mL in men >60 years and <35 years, respectively). Paradoxically, leptin concentration was elevated in heart failure, caused entirely by reduced renal clearance of leptin release, 142.0+/-30.5 mL/min, compared with 56.9+/-18.9 mL/min (P<0.05). These results provide some support for the view that leptin stimulates the sympathetic nervous system, at least for renal sympathetic outflow, but do not confirm the concept of regulatory feedback inhibition of leptin release by the sympathetic nervous system.
 ...
PMID:Interactions between leptin and the human sympathetic nervous system. 1266 87

Expression of cardiac and gastric ghrelin messenger (m) RNA, together with heart and body weights, were measured in leptin-deficient (ob) and leptin receptor-deficient (db) mice with heart failure induced by viral myocarditis. Significant elevations in cardiac ghrelin mRNA levels and heart weight were observed in ob and db mice 10 days after viral inoculation compared with baseline values. Expression of gastric ghrelin mRNA was not upregulated in ob and db mice on day 10. The elevated expression of cardiac ghrelin mRNA seems to compensate for the lack of upregulation in gastric ghrelin mRNA.
 ...
PMID:Upregulation of cardiac ghrelin mRNA in leptin-deficient and leptin receptor-deficient mice with viral myocarditis. 1470 15

Obesity is a major risk factor for the development of heart failure. Importantly, it is now appreciated that a change in the number of myocytes is one of multiple structural and functional alterations (remodeling) leading to heart failure. Here we investigate the effect of leptin, the product of the obese (ob) gene, on proliferation of human and murine cardiomyocytes. Leptin caused a time- and dose-dependent significant increase in proliferation of HL-1 cells that was inhibited by preincubation with PD98059 and LY294002, suggesting that leptin mediated proliferation via extracellular signal-regulated kinase-1/2- and phosphatidylinositol-3-kinase-dependent signaling pathways. We confirmed that leptin activates both extracellular signal-regulated kinase-1/2 phosphorylation and association of phosphatidylinositol-3-kinase (regulatory p85 subunit) with phosphotyrosine immunoprecipitates. We also examined bromodeoxyuridine incorporation as a measure of new DNA synthesis and demonstrated a stimulatory effect of leptin in both HL-1 cells and human cardiomyocytes. Bromodeoxyuridine incorporation in HL-1 cells was inhibited by PD98059 and LY294002. Our results establish a mitogenic effect of leptin in cardiomyocytes and provide additional evidence for a potential direct link between leptin and cardiac remodeling in obesity.
 ...
PMID:Leptin increases cardiomyocyte hyperplasia via extracellular signal-regulated kinase- and phosphatidylinositol 3-kinase-dependent signaling pathways. 1471 11

Arterial hypertension is one of the major risk factors in cardiovascular and renal disease. Advances in the study of pathophysiologic mechanisms and the relationship between several regulatory systems provide the basis for development of more selective therapeutic strategies. The increasing understanding of the role played by ETs, natriuretic peptides, AM, and leptin opens new frontiers in the care of hypertension and its complications, coronary artery disease and heart failure and other forms of cardiovascular disease.
 ...
PMID:Significance of recently identified peptides in hypertension: endothelin, natriuretic peptides, adrenomedullin, leptin. 1487 Oct 50

Obesity is a significant health problem due to its serious medical complications that include hypertension, insulin resistance, diabetes, coronary artery disease, and heart failure. This review addresses the hypothesis that stearoyl-CoA desaturase (SCD) is an important metabolic control point in body weight regulation. SCD is the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids. These products are the most abundant fatty acids found in triglycerides, cholesterol esters, wax esters, and phospholipids. Mice with a disruption in the scd1 gene (scd1(-/-)) have increased energy expenditure, reduced body adiposity, and increased insulin sensitivity, and are resistant to diet-induced obesity. The expression of several genes encoding enzymes of lipid oxidation is upregulated, whereas genes encoding enzymes of lipid synthesis are down regulated in the scd1-deficient mice. scd1 is also a component of the novel metabolic response to the hormone leptin. SCD therefore appears to be an important metabolic control point, and inhibition of its expression could be of benefit in the treatment of obesity, diabetes, cardiovascular disease, and other metabolic diseases.
 ...
PMID:The role of stearoyl-CoA desaturase in body weight regulation. 1503 Jul 94

Endothelins are a family of three peptides of 21 amino acids with strong vasoconstrictor effects. The three peptides are encoded by three different genes and derived from precursors (" big endothelins") which are cleaved by metalloproteases, named endothelin-converting enzyme. Two receptors have been cloned, ET-A and ET-B which bind the three endothelins with various affinities. The diverse expression pattern of the endothelin system (ET) components is associated with a complex pharmacology and its counteracting physiological actions. New modulators of the ET system have been described : retinoic acid, leptin, prostaglandins, hypoxia. Endothelins can be considered as regulators working in paracrine and autocrine fashion in a variety of organs in different cellular types. The ET system has beneficial and detrimental roles in mammals. The different components have been shown to be essential for a normal embryonic and neonatal development, for renal homeostasis and maintenance of basal vascular tone. They are involved in physiological and tumoral angiogenesis. They affect the physiology and pathophysiology of the liver, muscle, skin, adipose tissue and reproductive tract. The endothelin system participates in the development of atherosclerosis as well as pulmonary hypertension, and mediates cardiac remodeling in heart failure. Elaboration of new animal models (knock-out, pathophysiological models em leader ) will allow the clear genetic dissection of physiological and pathophysiological roles of the endothelin system.
 ...
PMID:[What is the role of endothelin system?]. 1506 80


1 2 3 4 5 6 7 8 9 10 Next >>