The relationship between tumor necrosis factor-α, brain natriuretic peptide and atrial natriuretic peptide in patients with chronic heart failure
Cytokines such as tumor necrosis factor-alpha (TNF) contribute to cardiac dysfunction in chronic heart failure (CHF). Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) are thought to reflect cardiac functional and structural damage. To study the relationship between BNP, ANP, and TNF, these parameters were measured in fasting venous blood samples of 25 CHF patients (age 66+/-2 years, pVO(2) 17.4+/-2.1 mL/kg/min, NYHA class 2.8+/-0.2, all mean+/-SEM) and 8 healthy controls (age 71+/-2 years). Patients with CHF had higher plasma levels of BNP (p<0.05), ANP (p<0.05), norepinephrine (p<0.01), and echocardiographic left ventricular end-diastolic diameter (LVEDD, p<0.05) compared to controls, whereas TNF and epinephrine were not significantly different. There were significant correlations between natriuretic peptides and markers of inflammation and myocardial dysfunction in CHF patients: BNP vs. TNF (r=0.64, p=0.0006), vs. LVEDD (r=0.59, p=0.0025); ANP vs. TNF (r=0.60, p=0.0016), vs. LVEDD (r=0.65, p=0.0006); TNF vs. LVEDD (r=0.57, p=0.004). After adjustment for NYHA, creatinine clearance, and age TNF correlated with BNP (all p=0.01) and ANP (all p<0.002). The cachectic CHF patients (n=7,>6% weight loss) had the highest BNP (p<0.001 vs. controls, p<0.05 vs. non-cachectic CHF) and ANP levels (p=0.01 vs. controls). Concentrations of uric acid, epinephrine, and norepinephrine also correlated with ANP and BNP. In CHF, TNF is closely related to BNP and ANP (independently of CHF severity and ventricular dysfunction), particularly in patients with cardiac cachexia. TNF may causally contribute to intrinsic cardiac dysfunction thereby stimulating BNP and ANP secretion.
[Show abstract] [Hide abstract] ABSTRACT: The present study was taken as an effort to assess the effects of paeonol on diabetic cardiomyopathy. Diabetes was induced in separate groups of Sprague-Dawley rats using streptozotocin. Treatment group animals received paeonol (50, 100 or 200 mg/kg body weight/day; orally) 5 weeks after streptozotocin induction for 6 weeks. Paeonol strikingly reduced myocardial apoptosis and improved cardiac function and myocardial architecture. Serum levels of glucose, reactive oxygen species and inflammatory mediators (TNF-α, IL-6 and IL-1β) were significantly reduced with decreased accumulation of collagen in the cardiac tissue. Paeonol modulated p-Akt, glycogen synthase kinase-3β and glycogen synthase, while significantly down-regulated protease-activated receptor-1, caspase-3, TNF-α, NF-κB p65, and p-Iκ-Bα expressions. Paeonol effectively suppressed diabetic cardiomyopathy by improving myocardial function, regulating the inflammatory responses and Akt signalling.0Comments 0Citations
- "Expression of TNF-protein correlated with the serum levels. TNF-is an important pro-inflammatory cytokine and also a valuable marker in heart failure (Miettinen et al., 2008; Vaz Perez et al., 2010 ). Thus, significant reduction in the levels of and also ROS levels following paeonol treatment indicates the protective effects of paeonol on cardiac tissues in diabetes. "
[Show abstract] [Hide abstract] ABSTRACT: Introduction Toll-like receptor 4 (TLR4) is an innate immune receptor expressed in immune cells and the heart. Activation of the immune system following myocardial ischemia causes the release of proinflammatory mediators that may negatively influence heart function. Aim The aim of this study is to determine whether TLR4 is activated in peripheral monocytes and heart tissue taken from patients with varying degrees of myocardial dysfunction caused by coronary artery diseases and scheduled for coronary artery bypass graft (CABG) surgery before 12 months following operation. Methods and Results Patients (n=44) undergoing CABG surgery having left ventricular ejection fraction ≤ 45% (‘reduced EF’, n=20) were compared to patients with preserved EF >45% (‘preserved EF’ group, n=24). ‘Reduced EF’ patients exhibited increased TLR4 expression in monocytes (2.78±0.49 vs. 1.76±0.07 rMFI, p=0.03). Plasma levels of C-reactive protein, microRNA miR-320a, brain natriuretic peptide (pro BNP) and NADPH oxidase (NOX4) were also significantly different between the ‘preserved EF’ and ‘reduced EF’groups. Elevated TLR4 gene expression levels in the right auricle correlated with those of EF (p<0.008), NOX4 (p<0.008) and miR320, (p<0.04). In contrast, no differences were observed in peripheral monocyte TLR2 expression. After CABG surgery, monocyte TLR4 expression decreased in all patients, reaching statistical significance in the ‘reduced EF’ group. Conclusion TLR4 is activated in peripheral monocytes and heart tissue obtained from patients with ischemic heart disease and reduced left ventricular function. Coronary revascularization decreases TLR4 expression. We therefore propose that TLR4 plays a pathogenic role and may serve as an additional marker of ischemic myocardial dysfunction.0Comments 0Citations
- "Several studies have demonstrated that the innate immune system is associated with the development of heart failure (HF)[1,5] . It has also been reported that levels of the cardiodepressant cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) are elevated in peripheral blood mononuclear cells of patients with HF . These cytokines can be produced by marginating and infiltrating monocytes and may contribute to the inflammatory and subsequent immune responses undergoing HF [7,8]. "
[Show abstract] [Hide abstract] ABSTRACT: Heart failure (HF) with preserved ejection fraction (HFPEF) is an increasingly prevalent clinical syndrome with many unresolved issues regarding diagnosis, pathophysiology, and treatment. The major pathophysiological mechanisms underlying HFPEF are known to be fibrosis and reduced ventricular compliance, and hypertension (HTN) is perhaps the most significant risk factor for the development of left ventricular diastolic dysfunction (LVDD). Inflammation is one of the earliest events in cardiac stress situations such as pressure and/or volume overload and involves elevated levels of endothelial adhesion molecules as well as increased production and release of inflammatory cytokines and chemokines in the tissue. The latter promotes the infiltration of activated inflammatory cells, particularly monocytes, into the cardiac tissue. Increased monocyte infiltration is seen in the early and late stages of HTN and HFPEF. Once inside the tissue, monocytes differentiate into macrophages and promote cardiac inflammation, tissue injury, and myocardial fibrosis. This review focuses on inflammation as the initial and primary trigger of ventricular remodelling in HTN and LVDD, affecting progression to HFPEF. The link between inflammation and b-type natriuretic peptide (BNP), a clinical marker of cardiac pressure overload which is positively associated with cardiac dysfunction and HF, is also described. Finally, current and prospective therapeutic approaches for HFPEF based on modification of the inflammatory response are reviewed.0Comments 21Citations
- "BNP and IL6 gene levels were consistently elevated in cardiac hypertrophy complicated with diastolic LV dysfunction in spontaneously hypertensive rats, indicating active inflammatory processes in these hearts . Additionally, a significant correlation between IL6, BNP, and LV end-diastolic dimension (LVEDD) values was found in patients with idiopathic LV dysfunction  and elevated BNP correlated with TNF and LVEDD in chronic HF patients . Ahmad et al.  also identified an association between TNFa, IL6, NT-proBNP, and LV function recovery in patients with dilated cardiomyopathy. "