Cellular Basis for Therapeutic Choices in Heart Failure

Opie, Lionel H.

doi:10.1161/01.cir.0000146803.14063.f7

Cited by 20 publications

(17 citation statements)

References 33 publications

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“…Left ventricular failure is generally associated with an increase in sympathetic activity and downregulation of the beta-adrenergic receptors [16]. This receptor is also downregulated in Table 4 Bivariate predictors of death or need for transplantation in children.…”

Section: Discussionmentioning

confidence: 99%

Heart rate variability predicts outcome in children with pulmonary arterial hypertension

Lammers

Munnery

Hislop³

et al. 2010

International Journal of Cardiology

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Section: Discussionmentioning

confidence: 99%

Heart rate variability predicts outcome in children with pulmonary arterial hypertension

Lammers

Munnery

Hislop³

et al. 2010

International Journal of Cardiology

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“…19,20 This is in addition to a reversal of the fetal gene program, which has previously been observed with S100A1 overexpression in myocytes and is in agreement with previous reports showing reverse remodeling of failing and infarcted myocardium in vivo after adenoviral S100A1 gene transfer. 6,15,21 Similarly, apoptosis, thought to contribute to the progressive deterioration of contractile function through "dropout" of cardiomyocytes, 22 was minimized in STG-MI remote myocardium. Several previously reported mechanisms might contribute at least in part to this effect.…”

Section: Discussionmentioning

confidence: 99%

“…22 In contrast, favorable hemodynamic effects in STG-MI were translated into superior survival. This is important to note because other strategies targeting SR Ca 2ϩ cycling, eg, by means of SERCA2 gene addition, can result in impaired survival in response to ischemic cardiac injury.…”

Section: Discussionmentioning

confidence: 99%

Cardiac S100A1 Protein Levels Determine Contractile Performance and Propensity Toward Heart Failure After Myocardial Infarction

et al. 2006

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Background— Diminished cardiac S100A1 protein levels are characteristic of ischemic and dilated human cardiomyopathy. Because S100A1 has recently been identified as a Ca 2+ -dependent inotropic factor in the heart, this study sought to explore the pathophysiological relevance of S100A1 levels in development and progression of postischemic heart failure (HF). Methods and Results— S100A1-transgenic (STG) and S100A1-knockout (SKO) mice were subjected to myocardial infarction (MI) by surgical left anterior descending coronary artery ligation, and survival, cardiac function, and remodeling were compared with nontransgenic littermate control (NLC) and wild-type (WT) animals up to 4 weeks. Although MI size was similar in all groups, infarcted S100A1-deficient hearts (SKO-MI) responded with acute contractile decompensation and accelerated transition to HF, rapid onset of cardiac remodeling with augmented apoptosis, and excessive mortality. NLC/WT-MI mice, displaying a progressive decrease in cardiac S100A1 expression, showed a later onset of cardiac remodeling and progression to HF. Infarcted S100A1-overexpressing hearts (STG-MI), however, showed preserved global contractile performance, abrogated apoptosis, and prevention from cardiac hypertrophy and HF with superior survival compared with NLC/WT-MI and SKO-MI. Both Gq-protein–dependent signaling and protein kinase C activation resulted in decreased cardiac S100A1 mRNA and protein levels, whereas Gs-protein–related signaling exerted opposite effects on cardiac S100A1 abundance. Mechanistically, sarcoplasmic reticulum Ca 2+ cycling and β-adrenergic signaling were severely impaired in SKO-MI myocardium but preserved in STG-MI. Conclusions— Our novel proof-of-concept study provides evidence that downregulation of S100A1 protein critically contributes to contractile dysfunction of the diseased heart, which is potentially responsible for driving the progressive downhill clinical course of patients with HF.

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“…As low T3 and fT3 are independent predictors of death in the general population [7–9], it has been suggested that the thyroid system can also play a role in the development of cardiac disease. Indeed, decreased active thyroid hormone levels are considered to be part of the deranged neuroendocrine/proinflammatory system that is associated with CHF [10]. This proinflammatory stimuli and in particular interleukin (IL) signalling, has been reported to downregulate the peripheral conversion of total thyroxine (T4) into T3 in both experimental [11, 12] and clinical studies [13, 14].…”

Section: Introductionmentioning

confidence: 99%

Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease

Carrero

Qureshi

Axelsson

et al. 2007

Journal of Internal Medicine

159

123

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AB, Novum, Huddinge; Sweden). Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease. J Intern Med 2007; 262: 690-701.Objectives. In this study, we explore the associations of decreased thyroid hormone levels with inflammation, wasting and survival in biochemically euthyroid patients with end-stage renal disease (ESRD).Design. After exclusion of 23 patients with thyroidstimulating hormone (TSH) values outside the normal range (0.1-4.5 mIU L )1 ), 187 clinically and biochemically euthyroid incident ESRD stage 5 patients starting dialysis were followed for a median of 20 (range 1-60) months. Measurements of total and free forms of thyroid hormones, s-albumin, hs-CRP, interleukin (IL)-6, vascular adhesion molecule (VCAM)-1 and insulin-like growth factor 1 (IGF-1) were performed at baseline.Results. In this population, 17 out of 210 patients (8%) were defined as subclinically hypothyroid. Multivariate analysis, according to receiver operating characteristic (ROC) curves, showed that mortality was best predicted by total triiodothyronine (T3). When using the cut-off levels derived from ROC, low T3 levels were associated with increased inflammation (higher hs-CRP, IL-6 and VCAM-1) and lower concentration of both s-albumin and IGF-1. Finally, low T3 but not low free triiodothyronine was associated with worse all-cause (Likelihood ratio = 45.4; P < 0.0001) and cardiovascular mortality (Likelihood ratio = 47.8; P < 0.0001) after adjustment for confounding factors.Conclusion. This study showed that low T3 levels are independent predictors of all-cause and also cardiovascular disease mortality in biochemically euthyroid patients, perhaps due to an intimate association with inflammation. Based on these results, the use of T3 levels in studies assessing the relationship between thyroid dysfunction and mortality risk is recommended.

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Cellular Basis for Therapeutic Choices in Heart Failure

Cited by 20 publications

References 33 publications

Heart rate variability predicts outcome in children with pulmonary arterial hypertension

Heart rate variability predicts outcome in children with pulmonary arterial hypertension

Cardiac S100A1 Protein Levels Determine Contractile Performance and Propensity Toward Heart Failure After Myocardial Infarction

Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease

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