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)

Thyroid hormone deficiency has profound effects on the cardiovascular system, resulting in decreased cardiac contractility, adrenergic responsiveness, and vascular volume and increased peripheral vascular resistance. To determine the importance of direct cardiac effects in the genesis of hypothyroid cardiac dysfunction, the cardiac myocyte was specifically targeted with a mutant thyroid hormone receptor (TR)-beta (Delta337T-TR-beta(1)) driven by the alpha-myosin heavy chain (alpha-MHC) gene promoter. As a control in these experiments, a wild-type (Wt) TR-beta(1) was also targeted to the heart by using the same promoter. Transgenic mice expressing the mutant TR displayed an mRNA expression pattern consistent with cardiac hypothyroidism, even though their peripheral thyroid hormone levels were normal. When these animals were rendered hypothyroid or thyrotoxic, mRNA expression of MHC isoforms remained unchanged in the hearts of the Delta337T transgenic animals, in contrast to Wt controls or transgenic animals expressing Wt TR-beta(1), which exhibited the expected changes in steady-state MHC mRNA levels. Studies in Langendorff heart preparations from mutant TR-beta(1) transgenic animals revealed evidence of heart failure with a significant reduction in +dP/dT, -dP/dT, and force-frequency responses compared with values in Wt controls and transgenic mice overexpressing the Wt TR-beta(1). In contrast, in vivo measures of cardiac performance were similar between Wt and mutant animals, indicating that the diminished performance of the mutant transgenic heart in vitro was compensated for by other mechanisms in vivo. This is the first demonstration indicating that isolated cardiac hypothyroidism causes cardiac dysfunction in the absence of changes in the adrenergic or peripheral vascular system.
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PMID:Cardiac dysfunction caused by myocardium-specific expression of a mutant thyroid hormone receptor. 1074 7

Evaluation of: Jankowska EA, Biel B, Majda J et al. : Anabolic deficiency in men with chronic heart failure; prevalence and detrimental impact on survival. Circulation 114, 1829-1837 (2006). The study examined the circulating levels of three anabolic hormones (testosterone, insulin-like growth factor-1 and dehydroepiandrosterone sulfate) in 208 men with stable chronic heart failure and 366 healthy controls. A high prevalence of anabolic hormone deficiency (89% deficient in one or more hormone) was found in heart failure patients. Hormone levels were weakly related to disease severity and hormone deficiency independently predicted prognosis (a 3-year survival rate of 27% was found in subjects deficient in all three hormones). Although it cannot be concluded that anabolic hormone deficiency contributes to the disease process - it may simply reflect chronic disease with no physiological consequence - it is highly plausible that deficiency may at least contribute to symptomatology. Further studies evaluating anabolic hormone replacement for symptomatic improvement and possible prognostic benefit are warranted.
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PMID:Metabolic perturbation in chronic heart failure: time to redress the balance? 1980 40

The phospholipase neutral sphingomyelinase (N-SMase) has been recognized as a major mediator of processes such as inflammation, development and growth, differentiation and death of cells, as well as in diseases such as Alzheimer's, atherosclerosis, heart failure, ischemia/reperfusion damage, or combined pituitary hormone deficiency. Although activation of N-SMase by the proinflammatory cytokine TNF was described almost two decades ago, the underlying signaling pathway is unresolved. Here, we identify the Polycomb group protein EED (embryonic ectodermal development) as an interaction partner of nSMase2. In yeast, the N terminus of EED binds to the catalytic domain of nSMase2 as well as to RACK1, a protein that modulates the activation of nSMase2 by TNF in concert with the TNF receptor 1 (TNF-R1)-associated protein FAN. In mammalian cells, TNF causes endogenous EED to translocate from the nucleus and to colocalize and physically interact with both endogenous nSMase2 and RACK1. As a consequence, EED and nSMase2 are recruited to the TNF-R1.FAN.RACK1-complex in a timeframe concurrent with activation of nSMase2. After knockdown of EED by RNA interference, the TNF-dependent activation of nSMase2 is completely abrogated, identifying EED as a protein that both physically and functionally couples TNF-R1 to nSMase2, and which therefore represents the "missing link" that completes one of the last unresolved signaling pathways of TNF-R1.
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PMID:The Polycomb group protein EED couples TNF receptor 1 to neutral sphingomyelinase. 2008 May 39

Clinical presentation of hypopituitarism in the neonate may be variable, ranging from absent to severe nonspecific symptoms and may be life-threatening in patients with adrenocorticotropic hormone deficiency. The LIM homeobox gene 4 (LHX4) transcription factor regulates early embryonic development of the anterior pituitary gland. Autosomal dominant mutations in LHX4 cause congenital hypopituitarism with variable combined pituitary hormone deficiency (CPHD). We report on a neonate with unexplained heart failure and minor physical anomalies, suggesting a midline defect. She was diagnosed with complete CPHD. Cardiac function was rescued by replacement with hydrocortisone and thyroxine; hypoglycaemia stopped under growth hormone therapy. Magnetic resonance imaging revealed a dysgenetic pituitary gland suggesting an early developmental defect. Array comparative genomic hybridization showed a maternally inherited 1.5-megabase microdeletion in 1q25.2q25.3, including the LHX4 gene. Haploinsufficiency of LHX4 likely explains the predominant pituitary phenotype in the proposita and we suggest variable intrafamilial penetrance of the inherited microdeletion. To the best of our knowledge, we are the first to report on heart failure as a rare nonspecific symptom of treatable CPHD in the newborn. Variably penetrant pituitary insufficiency, including this severe and atypical presentation, can be correlated with LHX4 insufficiency and highlights the role of LHX4 for pituitary development.
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PMID:Panhypopituitarism presenting as life-threatening heart failure caused by an inherited microdeletion in 1q25 including LHX4. 2223 9

It is well established that thyroid hormones affect the cardiovascular system through genomic and nongenomic actions. TRalpha1 is the major thyroid hormone receptor in the heart. T3 suppresses increased mitotic activity of stimulated cardiomyocytes. Hyperthyroidism induces a hyperdynamic cardiovascular state, which is associated with enhanced left ventricular systolic and diastolic function and the chronotropic and inotropic properties of thyroid hormones. Hypothyroidism, however, is characterized by opposite changes. In addition, thyroid hormones decrease peripheral vascular resistance, influence the rennin-angiotensin system (RAS), and increase blood volume and erythropoetin secretion with subsequent increased preload and cardiac output. Thyroid hormones play an important role in cardiac electrophysiology and have both pro- and anti-arrhytmic potential. Thyroid hormone deficiency is associated with a less favorable lipid profile. Selective modulation of the TRbeta1 receptor is considered as a potential therapeutic target to treat dyslipidemia without cardiac side effects. Thyroid hormones have a beneficial effect on limiting myocardial ischemic injury, preventing and reversing cardiac remodeling and improving cardiac hemodynamics in endstage heart failure. This is crucial because a low T3 syndrome accompanies both acute and chronic cardiac diseases.
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PMID:[Thyroid hormone and the cardiovascular system]. 2534 79

Sheehan's syndrome (SS) develops as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage and is characterized by various degrees of hypopituitarism. Although the occurrence of SS is now rare, it should still be considered in any woman with a history of peripartum hemorrhage who develops manifestations of pituitary hormone deficiency any time following the event. Appropriate hormone replacement therapy results in marked clinical improvement. We present an unusual case of SS in a young lady who continued to have normal menstruation after the index event, had two spontaneous pregnancies, and was diagnosed only 11 years later when she presented to us with acute heart failure.
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PMID:Hypopituitarism presenting as congestive heart failure. 2827 76

Heart failure (HF) is a disease characterized by increasing prevalence, huge direct and indirect costs, and an ominous prognosis, worse than many cancers. At the beginning of the 90s, growth hormone (GH) was proposed as potential adjunctive therapy in HF mostly due to its growth-promoting, vasodilating, and anti-apoptotic actions. However, although several uncontrolled clinical studies showed that GH therapy improved several cardiovascular parameters, two robust trials failed to confirm these findings. Dwelling upon potential explanations for such apparent discrepancy led to the hypothesis that HF patients exhibit an inhomogeneous basal activity of the GH/insulin-like growth factor 1 (IGF-1) axis, ranging from GH/IGF-1 deficiency to GH resistance. This complex phenomenon was then reconsidered in the context of the so-called multiple hormone deficiency syndrome (MHD), that is the recognition that HF is characterized not only by the hyperactivation of several signaling pathways including the adrenergic, the renin-angiotensin-aldosterone and cytokine systems, but also by a reduced anabolic drive leading to a state of anabolic/catabolic imbalance. Mounting evidence support the concept that such imbalance is not a mere epiphenomen, since it exerts a significant impact on clinical performance and more importantly, on survival. Therefore, the paradigm shift to reconsider HF as MHD represented the underpinning to implement clinical trials focused on hormone replacement therapies in congestive heart failure (CHF). With regard to GH replacement therapy, one controlled single-blind study yielded promising results, and we are currently conducting a double-blind controlled trial, as well a large Registry study to evaluate the impact of MHD on HF progression.
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PMID:Growth hormone in heart failure revisited: An old story retold. 3018 59

The model used to explain the pathophysiologic substrate and progressive worsening in chronic heart failure (CHF) is based on the hyperactivity of renin-angiotensin-aldosterone system and adrenergic pathway. Although the neurohormonal medical approach has many advantages, it has several pitfalls, as demonstrated by high rates of CHF mortality and hospitalization. A growing body of evidence has led to the hypothesis that CHF is a multiple hormone deficiency syndrome, characterized by a reduced anabolic drive that has relevant functional and prognostic implications. The aim of this review is to summarize the evidence of reduced drive of main anabolic axes in CHF.
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PMID:Prognostic Value of Hormonal Abnormalities in Heart Failure Patients. 3107 95

A growing body of evidence led to the hypothesis that heart failure (HF) could be considered a multiple hormone deficiency syndrome. Deficiencies in the main anabolic axes cannot be considered as mere epiphenomena, are very common in HF, and are clearly associated with poor cardiovascular performance and outcomes. Growth hormone deficiency and testosterone deficiency play a pivotal role and the replacement treatment is an innovative therapy that should be considered. This article appraises the current evidence regarding growth hormone and testosterone deficiencies in HF and reviews novel findings about the treatment of these conditions in HF.
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PMID:Hormonal Replacement Therapy in Heart Failure: Focus on Growth Hormone and Testosterone. 3107 96