Background: Circulating soluble (s) cell adhesion molecules (CAMs) are elevated in patients with congestive heart failure (CHF) and may play an important role in the pathogenesis of CHF by mediating the cell-cell interactions of the immune response. However, clinical data about the prognostic value of sCAMs are sparse. The purpose of this study is to determine whether various sCAMs can provide prognostic information in patients with CHF. Methods: We measured circulating levels of three sCAMs (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and sP-selectin) in 74 patients with symptomatic chronic CHF and left ventricular ejection fraction (LVEF) -50%. We compared these levels with those of a group of 19 age-matched control subjects. Major adverse cardiac events (death, heart transplantation or hospitalization with worsening CHF) during a median follow-up period of 240 days were determined. Results: The concentrations of the three sCAMs in the 74 patients with CHF were significantly associated with one another. Their levels were higher than those of the control subjects and increased with the severity of CHF. Significantly higher sCAM levels were noted in those patients who had major adverse cardiac events during the follow-up period. There were significant negative correlations between LVEF and sCAMs. However, only high levels of sP-selectin were found to be an independent significant predictor of CHF by Cox proportional hazards analysis. Conclusions: These findings indicate that the levels of these three sCAMs increase with the severity of CHF and are related to clinical outcomes. Among them, high levels of sP-selectin can provide prognostic information independently in patients with CHF.
Objectives: Endothelin-1 (ET-1) induces cardiac hypertrophy, whereas adiponectin may elicit protective effects in the vasculature and myocardium. We therefore evaluated the relationship between plasma ET-1 and adiponectin levels in heart failure (HF) patients, and the association between adiponectin expression and ET-1-induced hypertrophy of human cardiomyocytes (HCM) in vitro. Methods: One hundred seventeen patients with chronic HF were enrolled into this study. A group of 7 patients with end-stage HF undergoing heart transplantation was included in the histopathological study. Baseline clinical evaluations and laboratory measurements were performed. HCM cultures were studied to investigate the effect of ET-1 on cell size and adiponectin expression. Results: Plasma ET-1, adiponectin, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) increased with the severity of HF. Higher New York Heart Association functional class, plasma ET-1, adiponectin, and NT-proBNP levels were significant predictors of adverse outcomes in these patients. The myocardial expression of adiponectin was significantly higher in the recipient hearts of patients undergoing emergency or urgent heart transplantation. In cell culture, ET-1 significantly increased cell size and adiponectin expression in HCM. Conclusions: Adiponectin was significantly elevated in HF and was significantly associated with ET-1. The study provides a basis for further investigation of ET-1 and adiponectin modulation as a therapeutic strategy for ventricular remodeling in HF.
The fenofibrate directly inhibits monocyte binding by TNF-alpha-activated HAECs, probably through preventing up-regulation of cell adhesion molecules by endothelial cells in response to inflammatory stimuli. This PPARalpha activator may have the potential to ameliorate vascular inflammation in patients with CHF.
Our results parallel the demonstration of a U-shaped relationship between alcohol consumption and cardiovascular mortality, and suggest that anti-inflammatory effects of moderate alcohol intake may partly be linked to a low cardiovascular and overall mortality.
Aim: Previous studies demonstrated that endothelin-1 (ET-1) can significantly increase the cell size and stimulate adiponectin expression in cultured human cardiomyocytes (HCM). The aim of the present study was to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor-α (PPARα) activator, on cell hypertrophy and adiponectin expression in vitro and in a rat model of daunorubicin-induced cardiomyopathy.Methods: The cultured human cardiomyocytes (HCM) were stimulated with or without ET-1. The cell size and the protein expressions of PPARα and adiponectin were tested by confocal Immunofluorescence study and Western blot, respectively. To study the effects of PPARα activation on ET-1-induced cell hypertrophy and adiponectin protein synthesis, HCM were pretreated with fenofibrate or small interfering RNA (siRNA) of PPARα. Echocardiographic parameters were measured and immunohistochemistry study of myocardial adiponectin expression was conducted in the in vivo study.Results: ET-1 significantly increased the cell size, dose-dependently suppressed the expression of PPARα, and enhanced the expression of adiponectin; whereas, such an increase of cell size and enhancement of adiponectin expression were inhibited by the pre-treatment with fenofibrate. Addition of siRNA of PPARα abolished the effects of fenofibrate. Moreover, we found that fenofibrate treatment can significantly improve the left ventricular function and reverse the myocardial expression of adiponectin.Conclusions: Our study shows that fenofibrate may protect against ET-1-induced cardiomyocyte hypertrophy and enhanced adiponectin expression through modulation of PPARα expression in vitro and limitation of daunorubicin cardiotoxicity in vivo, suggesting a novel mechanistic insight into the role of PPARα and adiponectin in cardiac hypertrophy and heart failure.
Peroxisome proliferator-activated receptor α (PPARα) plays a role in the pathogenesis of cardiac hypertrophy, although its underlying mechanism remains unclear. The purpose of this study was to evaluate the effect of PPARα activation on endothelin-1- (ET-1-) caused cardiomyocyte hypertrophy and explore its underlying mechanisms. Human cardiomyocytes (HCMs) were cultured with or without ET-1, whereafter the inhibitory effects of fenofibrate, a PPARα activator, on cell size and adiponectin protein were tested. We examined the activation of extracellular signal-regulated kinase (ERK) and p38 proteins caused by ET-1 and the inhibition of the ERK and p38 pathways on ET-1-induced cell size and adiponectin expression. Moreover, we investigated the interaction of PPARα with adiponectin and nuclear factor-κB (NF-κB) by electrophoretic mobility shift assays and coimmunoprecipitation. ET-1 treatment significantly increased cell size, suppressed PPARα expression, and enhanced the expression of adiponectin. Pretreatment with fenofibrate inhibited the increase in cell size and enhancement of adiponectin expression. ET-1 significantly activated the ERK and p38 pathways, whereas PD98059 and SB205380, respectively, inhibited them. Our results suggest that activated PPARα can decrease activation of adiponectin and NF-κB and inhibit ET-1-induced cardiomyocyte hypertrophy.
To achieve stable single-lead VDD pacing, a selection of the electrode with the optimal distance between the lead tip and the floating atrial dipole (AV distance [AVD]) is important. The authors hypothesized that the size of the right heart chambers may affect atrial sensing, and that measurement of their internal dimension at end-diastole (RHIDd) in the apical four chamber view by transthoracic echocardiography may aid in choosing the proper AVD. Twenty-six consecutive cases that had undergone VDD pacer implantation using the conventional chest X ray were examined retrospectively by the echocardiographic method. The chest x-ray method properly selected a lead with optimal atrial sensing, defined as minimum P wave amplitude > or = 1.0 mV, for only 20 (77%) of 26 patients. By comparing these results with their respective RHIDd, a cut-off point of 13 cm was obtained that indicated a criterion for choosing the proper AVD. The indication was that if the RHIDd was > or = 13 cm, a lead with an AVD of 15.5/16 cm should have been used; if the RHIDd was < 13 cm, a lead with an AVD of 13/13.5 cm should have been chosen. Using the echocardiographic method, all six patients who had suboptimal atrial sensing could be identified and classified as having missized (four undersized; two oversized) permanent leads. In conclusion, the described method provides a promising preoperative assessment of the best fitting electrode length in single lead VDD pacing. A prospective study is ongoing to verify its applicability.
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