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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The heart very often becomes a victim of endocrine abnormalities such as thyroid hormone imbalance and insulin deficiency, which are manifested in a broad spectrum of cardiac dysfunction from mildly compromised function to severe heart failure. These functional changes in the heart are largely independent of alterations in the coronary arteries and instead reside at the level of cardiomyocytes. The status of cardiac function reflects the net of underlying subcellular modifications induced by an increase or decrease in thyroid hormone and insulin plasma levels. Changes in the contractile and regulatory proteins constitute molecular and structural alterations in myofibrillar assembly, called myofibrillar remodeling. These alterations may be adaptive or maladaptive with respect to the functional and metabolic demands on the heart as a consequence of the altered endocrine status in the body. There is a substantial body of information to indicate alterations in myofibrillar proteins including actin, myosin, tropomyosin, troponin, titin, desmin, and myosin-binding protein C in conditions such as hyperthyroidism, hypothyroidism, and diabetes. The present article is focussed on discussion how myofibrillar proteins are altered in response to thyroid hormone imbalance and lack of insulin or its responsiveness, and how their structural and functional changes explain the contractile defects in the heart.
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PMID:Molecular defects in cardiac myofibrillar proteins due to thyroid hormone imbalance and diabetes. 1646 7

Experimental and clinical findings strongly support the concept that thyroid hormone (TU) has a fundamental role in the cardiovascular homeostasis both in physiological and pathological conditions. In heart failure (HF) the main alteration of the thyroid function is referred to as low-T3 syndrome characterized by the reduction in serum total T3 and free T3 with normal levels of thyroxine and thyrotropin. This syndrome, that affects one third of HF patients, is considered as adaptive factor minimizing catabolic phenomena of illness. However this interpretative hypothesis is actually questioned. In fact experimental data showed the potential effects of this syndrome in the progressive deterioration of cardiac function and myocardial remodeling of HF. Prognostic studies have shown that T3 levels represent a powerful predictor of mortality in HF patients, also adding prognostic power to conventional cardiac parameters. Large, multicenter, placebo controlled prospective studies will provide the safety and prognostic effects of the chronic treatment with thyroid hormones in HF.
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PMID:[Thyroid function and heart failure: from the new clinical evidences to the potential therapeutical implications]. 1649 59

The authors present the current knowledge on the intracellular mechanisms of thyroid hormone action in the cardiomyocytes. Many of the clinical manifestations of thyroid diseases are due to the ability of thyroid hormone to alter cardiovascular hemodynamics. Triiodothyronine affects the hemodynamic state mainly by its influence on the expression of cardiomyocyte genes. These genes encode both structural and regulatory proteins in the heart (myosin heavy chains, sarcoplasmic reticulum calcium-activated ATP-ase, phospholamban). The impaired myocardium contractile activity in hypothyreosis reminds findings in heart failure and may warrant further exploration of therapeutic approaches using thyroid hormone to improve cardiac function in heart failure.
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PMID:[Thyroid hormones and the cardiomyocytes]. 1677 90

Increased oxidative stress is involved in the pathogenesis of chronic heart failure (CHF), the common end result of most cardiac diseases. Selenium is an "essential" trace element, which means that it must be supplied by our daily diet and that its blood and tissue concentrations are extremely low. Selenium has a variety of functions. It is a key component of several functional selenoproteins required for normal health. The best known of these are the antioxidant glutathione peroxidase (GPx) enzymes, which remove hydrogen peroxide and the harmful lipid hydroperoxides generated in vivo by oxygen-derived species. GPx deficiency exacerbates endothelial dysfunction, a major contributing factor in the severity of CHF symptoms, in various conditions such as hyperhomocysteinemia. This suggests that homocysteine may be involved in the CHF associated endothelial dysfunction through a peroxide-dependent oxidative mechanism. Selenium also plays a role in the control of thyroid hormone metabolism and in protection against organic and inorganic mercury. One possible additional mechanism by which low selenium may compromise cardiovascular condition may be through the effect of selenium on the synthesis and activity of deiodinases, enzymes converting thyroxin into the biologically active triiodothyronine. Selenium and iodine actually interact in cardiovascular physiology, and further studies are needed to examine their role, in isolation and in association, in the development of CHF. Thus, selenium (through its role in selenoenzymes, thyroid hormones, and interactions with homocysteine and endothelial function) appears to be a major mediator in several pathways potentially contributing to CHF development.
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PMID:Selenium and antioxidant defenses as major mediators in the development of chronic heart failure. 1681 73

The sarcoplasmic reticulum (SR) plays a central role in the contraction and relaxation coupling in the myocardium. The SR Ca(2+)-ATPase (SERCA2) transports Ca(2+) inside the SR lumen during relaxation of the cardiac myocyte. It is well known that diminished contractility of the hypertrophic cardiac myocyte is the main factor of ventricular dysfunction in the failing heart. A key feature of the failing heart is a decreased content and activity of SERCA2, which is the cause of some of the physiological defects observed in the hypertrophic cardiomyocyte performance that are important during transition of compensated hypertrophy to heart failure. In this review different possible mechanisms responsible for decreased transcriptional regulation of the SERCA2 gene are examined, which appear to be the primary cause for decreased SERCA2 expression in heart failure. The experimental evidence suggests that several signalling pathways are involved in the downregulation of SERCA2 expression in the hypertrophic and failing cardiomyocyte. Therapeutic upregulation of SERCA2 expression using replication deficient adenoviral expression vectors, pharmacological interventions using thyroid hormone analogues, beta-adrenergic receptor antagonists, and novel metabolically active compounds are currently under investigation for the treatment of uncompensated cardiac hypertrophy and heart failure.
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PMID:Regulation of the sarcoplasmic reticulum Ca2+-ATPase expression in the hypertrophic and failing heart. 1690 96

Thyroid hormone metabolic disarray has been identified as a risk factor for the progression of heart disease and the development of heart failure (HF). Both hyper- and hypothyroidism have been associated with a failing myocardium. Poor cardiac contractility and low cardiac output due to hyperthyroidism is a rare occurrence and is mostly seen in patients with preexisting heart disease. Referred to as a "rate related" phenomenon, hyperthyroid-induced sustained sinus tachycardia or atrial fibrillation may further reduce ventricular contractility. Increasingly, the hypothyroid state, and in particular a low triiodothyronine level, has been associated with a reduced cardiac performance and poor prognosis in HF, even in the presence of normal thyroid-stimulating hormone levels. Low thyroid hormone levels alter cardiac gene expression and increase systemic vascular resistance, both resulting in a reduction of cardiac contractility and cardiac output. This review summarizes current data on thyroid dysfunction and HF as well as the emerging implications of the "low triiodothyronine state."
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PMID:Thyroid hormone and heart failure. 1691 3

Thyroid hormone-induced cardiac hypertrophy is similar to that observed in physiological hypertrophy, which is associated with high cardiac contractility and increased alpha-myosin heavy chain (alpha-MHC, the high ATPase activity isoform) expression. In contrast, angiotensin II (Ang II) induces an increase in myocardial mass with a compromised contractility accompanied by a shift from alpha-MHC to the fetal isoform beta-MHC (the low ATPase activity isoform), which is considered as a pathological hypertrophy and inevitably leads to the development of heart failure. The present study is designed to assess the effect of thyroid hormone on angiotensin II-induced hypertrophic growth of cardiomyocytes in vitro. Cardiomyocytes were prepared from hearts of neonatal Wistar rats. The effects of Ang II and 3,3',5-triiodo-thyronine (T3) on incorporations of [3H]-thymine and [3H]-leucine, MHC isoform mRNA expression, PKC activity, and PKC isoform protein expression were studied. Ang II enhanced [3H]-leucine incorporation, beta-MHC mRNA expression, PKC activity, and PKCepsilon expression and inhibited alpha-MHC mRNA expression in cardiomyocytes. T3 treatment prevented Ang II-induced increases in PKC activity, PKCepsilon, and beta-MHC mRNA overexpression and favored alpha-MHC mRNA expression. Thyroid hormone appears to be able to reprogram gene expression in Ang II-induced cardiac hypertrophy, and a PKC signal pathway may be involved in such remodeling process.
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PMID:Effects of triiodo-thyronine on angiotensin-induced cardiomyocyte hypertrophy: reversal of increased beta-myosin heavy chain gene expression. 1711 Oct 39

Pressure overload-induced cardiac hypertrophy leads to decreased contractile performance, frequently progressing to heart failure. Cardiac hypertrophy and heart failure can be accompanied by the so-called sick thyroid syndrome, resulting in decreased serum T(3) levels along with decreased expression of thyroid hormone receptors (TRalpha1 and TRbeta1) and sarco(endo)plasmic reticulum Ca-ATPase (SERCA). Because the binding of T(3) occupied receptors to the thyroid response elements in the SERCA promotor can increase gene expression, we wanted to determine whether increasing TR expression in the hypertrophied heart could also improve SERCA expression and cardiac function. Mice subjected to aortic constriction to generate pressure overload-induced hypertrophy were also subjected to gene therapy using adeno-associated virus (AAV) expressing either TRalpha1 or TRbeta1, with LacZ expressing AAV serving as control. After 8 wk of aortic constriction, a similar degree of hypertrophy was observed in all three groups; however, mice treated with TRalpha1 or TRbeta1 showed improved contractile function. Administration of a physiological dose of T(3) increased serum T(3) levels only into the lower range of normal. This T(3) dose, with or without AAV TR treatment, did not result in any significant increase in contractile performance. Calcium transients measured in isolated myocytes also exhibited an enhanced rate of decay associated with TRalpha1 or TRbeta1 treatment. Western blot analysis showed increased SERCA expression in the TRalpha1- or TRbeta1-treated groups relative to the LacZ-treated control group. These results demonstrate that increasing TR expression in the hypertrophied heart is associated with an improvement in contractile function and increased SERCA expression.
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PMID:Adeno-associated virus-mediated expression of thyroid hormone receptor isoforms-alpha1 and -beta1 improves contractile function in pressure overload-induced cardiac hypertrophy. 1731 66

This study assessed the behaviour of angiotensin II (Ang II) receptors in an experimental hypothyroidism model in male Wistar rats. Animals were subjected to thyroidectomy and resting for 14 days. The alteration of cardiac mass was evaluated by total heart weight (HW), right ventricle weight (RVW), left ventricle weight (LVW), ratio of HW, RVW and LVW to body weight (BW) and atrial natriuretic factor (ANF) expression. Cardiac and plasma Ang II levels and serum T3 and T4 were determined. The mRNA and protein levels of Ang II receptors were investigated by RT-PCR and Western blotting, respectively. Functional analyses were performed using binding assays. T3 and T4 levels and the haemodynamic parameters confirmed the hypothyroid state. HW/BW, RVW/BW and LVW/BW ratios and the ANF expression were lower than those of control animals. No change was observed in cardiac or plasma Ang II levels. Both AT1/AT2 mRNA and protein levels were increased in the heart of hypothyroid animals due to a significant increase of these receptors in the RV. Experiments performed in cardiomyocytes showed a direct effect promoted by low thyroid hormone levels upon AT1 and AT2 receptors, discarding possible influence of haemodynamic parameters. Functional assays showed that both receptors are able to bind Ang II. Herein, we have identified, for the first time, a close and direct relation of elevated Ang II receptor levels in hypothyroidism. Whether the increase in these receptors in hypothyroidism is an alternative mechanism to compensate the atrophic state of heart or whether it may represent a potential means to the progression of heart failure remains unknown.
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PMID:Cardiac angiotensin II type I and type II receptors are increased in rats submitted to experimental hypothyroidism. 1797 84

Thyroid hormone (TH) and insulin growth factor 1 (IGF1) systems both play crucial roles in the regulation of cardiac remodeling and hypertrophy processes. The mediation of this regulation is attributed to specific thyroid hormone receptors (TRs) and to the IGF1 receptor (IGF1R). In humans, two TR genes are expressed in the heart, TRalpha and TRbeta. Each gene generates two isoforms: TRalpha1, TRalpha2 and TRbeta1, TRbeta2. The aim of the present work was to study the local thyroid hormone and IGF1 signaling in human myocardium through the evaluation of the gene expression of TRalpha1, TRalpha2, TRbeta1 and IGF1R among atrial and ventricular biopsies obtained from patients undergoing cardiac surgery. Moreover, we evaluated possible correlations between TR and IGF1/IGF1R systems. Eighteen clinically and biochemically euthyroid patients (aged 68.3+/-3.2years, mean+/-SEM) without overt heart failure (Ejection Fraction (EF), 46.4+/-2.8%; Left Ventricular End Diastolic Diameter (LVEDD), 54.3+/-1.2mm, mean+/-SEM; NYHA I-II) were enrolled in the study: 13 undergoing aorto-coronary bypass and 5 undergoing valve replacement (aortic/mitral valve). The examination of total RNA, using real time PCR (LightCycler Technology) confirmed the expression of specific mRNAs encoding TRalpha1, TRalpha2, TRbeta1 and both IGF1 and IGF1R. We found that the three TR genes are co-expressed in the human atrium and ventricle. The finding of a strong correlation among IGF1R and the three TR genes expressed in the atrium (p<0.001) and among the three TRs in the atrium (p<0.001) suggests the interesting possibility that the two systems, TRs and IGF1R could also be functionally associated.
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PMID:Thyroid hormone receptor and IGF1/IGFR systems: possible relations in the human heart. 1756 Jul 56


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