Soluble Fms-like tyrosine kinase 1 is a novel predictor of brain natriuretic peptide elevation.

Soluble fms-like tyrosine kinase 1 (sFlt-1) is an endogenous inhibitor of vascular endothelial growth factor, which is involved in cardiovascular remodeling and atherosclerosis development. To examine the predictive role of sFlt-1 levels in patients with asymptomatic heart failure, we measured circulating sFlt-1 in patients with or without coronary artery disease (CAD). We analyzed 88 Japanese patients with CAD or patients at high risk for atherosclerosis and who were undergoing total risk management for cardiovascular disease prevention.

Effect of persistent activation of phosphoinositide 3-kinase on heart.

Aims: Insulin/insulin-like growth factor-1 (IGF-1) signaling plays an important role in many biological processes. The class IA isoform of phosphoinositide 3-kinase (PI3K) is an important downstream effector of the insulin/IGF-1 signaling pathway. The aim of this study is to examine the effect of persistent activation of PI3K on gene expression and markers of cellular senescence in murine hearts.

N-acetylcysteine suppresses the progression of ventricular remodeling in acute myocarditis: studies in an experimental autoimmune myocarditis (EAM) model.

Background: Electrical and structural remodeling, characterized by prolonged action potential duration (APD), Kv4.2 downregulation and cellular infiltration were studied in rat experimental autoimmune myocarditis (EAM). Because the reactive oxygen species (ROS) has been speculated to play a role in the promotion of such remodeling, the effect of N-acetylcysteine (NAC) on the progression of ventricular remodeling was evaluated.

Suppression of phosphoinositide 3-kinase prevents cardiac aging in mice.

Background: Heart failure is a typical age-associated disease. Although age-related changes of heart are likely to predispose aged people to heart failure, little is known about the molecular mechanism of cardiac aging.

Methods And Results: We analyzed age-associated changes in murine heart and the manner in which suppression of the p110alpha isoform of phosphoinositide 3-kinase activity modified cardiac aging.

Effects of ezetimibe add-on therapy for high-risk patients with dyslipidemia.

Background: Ezetimibe (Zetia) is a potent inhibitor of cholesterol absorption that has been approved for the treatment of hypercholesterolemia. Statin, an inhibitor of cholesterol synthesis, is the first-choice drug to reduce low-density lipoprotein-cholesterol (LDL-C) for patients with hypercholesterolemia, due to its strong effect to lower the circulating LDL-C levels. Because a high dose of statins cause concern about rhabdomyolysis, it is sometimes difficult to achieve the guideline-recommended levels of LDL-C in high-risk patients with hypercholesterolemia treated with statin monotherapy.

Angiotensin II receptor antagonist attenuates expression of aging markers in diabetic mouse heart.

Background: Diabetes mellitus is an independent risk factor for heart failure. Diabetes mellitus causes other age-related cardiovascular diseases. We assessed the hypothesis that hearts from diabetic animals are associated with accelerated aging processes.

Rapamycin ameliorates experimental autoimmune myocarditis.

Myosin-induced autoimmune myocarditis in rats is a model of human dilated cardiomyopathy. Rapamycin is a potent immunosuppressant and specifically inactivates the mammalian target of rapamycin (mTOR). To examine the role of mTOR in autoimmune myocarditis, we administered rapamycin to rats immunized with cardiac myosin.

C-reactive protein-induced production of interleukin-18 in human endothelial cells: a mechanism of orchestrating cytokine cascade in acute coronary syndrome.

The circulating interleukin (IL)-18 level is a strong predictor of death from cardiovascular causes in patients with coronary artery disease. However, the mechanisms of IL-18 in orchestrating the cytokine cascade and the accelerator of IL-18 production in atherosclerosis are still unknown. In the present study, we measured the serum concentration of IL-18 and other markers of inflammation in 35 patients with acute coronary syndrome.

Overexpression of tumor necrosis factor-alpha increases production of hydroxyl radical in murine myocardium.

Transgenic (TG) mice with cardiac-specific overexpression of tumor necrosis factor-alpha develop congestive heart failure with myocardial inflammation. The purpose of this study was to investigate the effects of tumor necrosis factor-alpha on reactive oxygen species (ROS) in this mouse model of cardiomyopathy. Myocardial production of hydroxyl radical detected by electron spin resonance spectroscopy was significantly increased in TG.

Immunomodulatory effect of pentoxifylline in suppressing experimental autoimmune myocarditis.

Although a recent clinical study reported the beneficial effects of pentoxifylline (PTX), a phosphodiesterase inhibitor, on both symptoms and cardiac function in dilated cardiomyopathy (DCM), the precise mechanism of the drug has not been delineated. This study examined the efficacy of PTX in the treatment of experimental autoimmune myocarditis (EAM), as a model of the autoimmune mechanism involved in DCM. Oral PTX, or saline as control, was administered to Lewis rats at 150mg/kg body weight per day bid daily from 5 days before immunization with cardiac myosin until death on Day 21.

Disruption of inducible nitric oxide synthase improves beta-adrenergic inotropic responsiveness but not the survival of mice with cytokine-induced cardiomyopathy.

Transgenic (TG) mice with cardiac-specific overexpression of tumor necrosis factor-alpha develop congestive heart failure. We have previously reported that short-term inhibition of inducible nitric oxide synthase (iNOS) ameliorates beta-adrenergic hyporesponsiveness in TG mice. To examine whether long-term inhibition of iNOS may rescue TG mice from developing congestive heart failure, we disrupted iNOS gene by crossing TG mice with iNOS knockout mice.

Involvement of inducible nitric oxide synthase in cardiac dysfunction with tumor necrosis factor-alpha.

Transgenic (TG) mice with cardiac-specific overexpression of tumor necrosis factor (TNF)-alpha develop dilated cardiomyopathy with myocardial inflammation. The purpose of this study was to investigate the role of nitric oxide (NO) in this mouse model of cardiomyopathy. Female TG and wild-type mice at the age of 10 wk were studied.

Circulating levels of interleukin 18 reflect etiologies of heart failure: Th1/Th2 cytokine imbalance exaggerates the pathophysiology of advanced heart failure.

Background: Proinflammatory cytokines such as tumor necrosis factor alpha play an important role in the pathophysiology of CHF. However, the mechanisms of immune activation in CHF remain unknown. Interleukin (IL)-18, a newly discovered cytokine with pleiotropic activities, is known to induce proinflammatory cytokines, chemokines, nitric oxide, and prostaglandins.