Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advanced glycation end products (AGEs) contribute significantly to diabetic complications, both macro- and microvascular. TRC4186 is an AGE-breaker that has been evaluated in vitro and in vivo and shown to reduce AGE burden. The aim of this study was to determine the effect of TRC4186 on diabetic cardiomyopathy and nephropathy in obese Zucker spontaneously hypertensive fatty rats (Ob-ZSF1), an animal model of diabetes with progressive cardiac and renal dysfunction. Ob-ZSF1 rats loaded with 0.5% salt were treated with TRC4186, 9 or 27 mg/kg twice daily intraperitoneally or vehicle control and monitored telemetrically throughout the study. Cardiac function was assessed terminally by Millar catheter. Markers of cardiac and renal dysfunction were measured and changes evaluated histopathologically. TRC4186 at 27 mg/kg prevented rise in blood pressure (BP) and also improved cardiac output (CO) secondary to better diastolic relaxation as well as systolic emptying in association with the reduction in afterload. At 9 mg/kg, CO was improved by compensatory increase in pre-load however afterload reduction was not adequate to allow efficient systolic emptying. Brain natriuretic peptide (BNP) and interleukin-6 (IL-6) expression was reduced with treatment. Deterioration in renal function was retarded as evident from albumin to creatinine ratio and renal histopathology. TRC4186, an AGE-breaker, clearly preserved cardiac function and reduced the severity of renal dysfunction in Ob-ZSF1, an animal model with persistent severe hyperglycemia leading to diabetic heart failure and renal failure.
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PMID:TRC4186, a novel AGE-breaker, improves diabetic cardiomyopathy and nephropathy in Ob-ZSF1 model of type 2 diabetes. 1954 15

Basic and clinical studies have suggested that inflammation predisposes to atrial fibrillation (AF). We assessed the association of 12 circulating inflammatory biomarkers (i.e., C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, osteoprotegerin, P-selectin, and tumor necrosis factor receptor II) with incident AF in 2863 Framingham Offspring Study participants (mean age 60.7 years, SD = 9.4, 55% women). During follow-up (median 6 years), 148 participants (43% women) developed incident AF. In the multivariable proportional hazards models, the inflammatory biomarker panel was associated with incident AF (p = 0.03). With stepwise selection (p <0.01 for entry and retention), log-transformed osteoprotegerin was associated with incident AF (hazard ratio per SD 1.30, 95% confidence interval 1.08 to 1.56, p = 0.006). Adjusting for interim myocardial infarction or heart failure attenuated the association between osteoprotegerin and incident AF (hazard ratio 1.18, 95% confidence interval 0.98 to 1.43, p = 0.09). In conclusion, circulating osteoprotegerin concentration was significantly associated with incident AF in our community-based sample, possibly mediated by interim cardiovascular events.
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PMID:Relation of multiple inflammatory biomarkers to incident atrial fibrillation. 1957 26

Heart failure is characterized by activation of the immune system which is strongly associated with disease severity and outcome. We sought to compare the prognostic impact of two established inflammatory markers - interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) - in patients with chronic heart failure. In stable, optimally managed outpatients with chronic heart failure, baseline levels of hsCRP and IL-6 were determined. Clinical follow-up was obtained and the rate of events (heart failure related deaths or hospitalizations) were recorded. We included 201 patients (32.7% female, NYHA class II [66.2%] or III [33.8%], mean age 70 years). During a median follow up of 614 (367-761) days, 64 (30.9%) patients experienced an event; those with an event had higher levels of hsCRP (median 2.93 [interquartile range 2.36-8.92] vs 2.23 [1.32-5.77] mmol/l) and IL-6 (7.8 [4.7-10.3] vs 4.3 [2.6-7.9] pg/ml). However, on Cox multivariate analysis, IL-6 but not hsCRP emerged as an independent predictor of prognosis (hazard ratio HR(adjusted) 2.74, 95% confidence interval 1.17-6.43; P = 0.020). Our findings suggest that IL-6 is a better prognostic predictor than hsCRP in patients with chronic stable heart failure.
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PMID:Interleukin-6 is a stronger prognostic predictor than high-sensitive C-reactive protein in patients with chronic stable heart failure. 1962 99

People with chronic obstructive pulmonary disease (COPD) suffer from muscle dysfunction which seems to be partly caused by systemic inflammation. Muscle protein breakdown as well as synthesis might be affected by this systemic inflammation. Additionally, it seems to induce excessive oxidative stress and reduce the level of growth-stimulating factors. As exercise training can have an anti-inflammatory effect in healthy people, the main question in this review is whether exercise (training) can also induce such effects in patients with COPD. However, because of the known inflammatory response after an acute bout of exercise, some researchers are afraid that exercise might actually worsen the inflammation in COPD. Recent evidence suggests, however, that the response might actually be anti-inflammatory and thus beneficial. Unfortunately, the evidence about the response of the inflammatory cytokines tumor necrosis factor-alpha and interleukin-6 to exercise in patients with COPD is inconsistent, making it impossible to conclude whether a single exercise bout is harmful or beneficial in patients with COPD. Long-term exercise training in healthy people as well as in patients with chronic heart failure, another chronic inflammatory disease, seems to have beneficial effects on the inflammatory response. In patients with COPD, however, no training-induced changes in cytokine levels have been found and it must be concluded that physical exercise training does not seem to have an anti-inflammatory effect in COPD. On the other hand, it does not have a proinflammatory effect, and since patients with COPD benefit from exercise training with regard to other health parameters it is still recommended that they exercise regularly.
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PMID:The potential anti-inflammatory effect of exercise in chronic obstructive pulmonary disease. 1967 44

We included 63 patients with chronic heart failure of ischemic origin (32 with left ventricular ejection fraction less than 40%) into prospective study with average duration of follow-up 27+/-10 months. Relative risk of lethal outcome was significantly increased in patients with initial endsystolic left ventricular dimension >6.0 m, enddiastolic left ventricular dimension >7.0 m, left atrial dimension >5.0 cm, left ventricular ejection fraction <35%, hemoglobin level <120 g/L, with disturbances of rhythm and conduction, and elevation of plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) >1000 mol/ml and interleukin-6 >20 g/ml. Relative risk of combined endpoint significantly increased at same values of echocardiographical parameters, plasma levels of NT-proBNP >500 mol/ml and interleukin-6 >10 g/ml.
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PMID:[Prognostic value of plasma levels of N-terminal pro-brain natriuretic peptide and proinflammatory cytokines in patients with heart failure of ischemic etiology]. 1984 14

Excessive immune activation and inflammatory mediators may play a critical role in the pathogenesis of chronic heart failure. Methotrexate is a commonly used anti-inflammatory and immunosuppressive drug. In this study, we used a rat model of cardiac myosin-induced experimental autoimmune myocarditis to investigate the effects of low-dose methotrexate (0.1 mg/kg/d for 30 d) on the plasma level of cytokines and cardiac remodeling and function. Our study showed that levels of tumor necrosis factor-(TNF-)alpha and interleukin-6 (IL-6) are significantly increased in postmyocarditis rats, compared with the control rats. Methotrexate treatment reduced the plasma levels of TNF-alpha and IL-6 and increased IL-10 level, compared to saline treatment. In addition, postmyocarditis rats showed significant cardiac fibrosis characterized by increased myocardial collagen volume fraction, perivascular collagen area, and the ratio of collagen type I to type III, compared with the control rats. However, MTX treatment not only markedly attenuated cardiac fibrosis, diminished the left ventricular end-diastolic dimension, but also increased the left ventricular ejection fraction and fractional shortening. Collectively, these results suggest that low-dose methotrexate has ability to regulate inflammatory responses and improves cardiac function and hence contributes to prevent the development of postmyocarditis dilated cardiomyopathy.
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PMID:Effects of methotrexate on plasma cytokines and cardiac remodeling and function in postmyocarditis rats. 1988 81

Cytokines play important roles in heart failure (HF). We examined whether cytokine levels are different in acute decompensated heart failure (ADHF) patients between with left ventricular systolic dysfunction (LVSDF) and with preserved LV ejection function (PLVEF). We studied 81 HF patients who were admitted to our hospital with acute decompensation. They were divided into two groups: LVSDF (LVEF)<45% and PLVEF (LVEF45%). Serum interleukin-6 (IL-6), highly sensitive C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-alpha), and IL-18 and plasma brain natriuretic peptide (BNP) were measured on admission and at discharge. On admission, IL-6 and hsCRP were higher in LVSDF than in PLVEF. IL-6 and hsCRP decreased after treatment in LVSDF, but not in PLVEF, while plasma BNP levels decreased in both HF with treatment. There was no difference in TNF-alpha or in IL-18 level between LVSDF and PLVEF, and they did not change after treatment in either group. In conclusion, cytokine profiles were different in ADHF between those with LVSDF and PLVEF. Activation of IL-6-hsCRP pathway may play a specific role in ADHF with LVSDF.
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PMID:Serum interleukin-6 and C-reactive protein are markedly elevated in acute decompensated heart failure patients with left ventricular systolic dysfunction. 2000 39

The role of inflammation in maintenance of paroxysmal atrial fibrillation (PAF) in patients with hypertension and no other heart disease has not been fully elucidated yet. We investigated the association of various inflammatory markers with cardioversion and recurrence of PAF in patients with hypertension. We studied 75 patients (44 male, mean age 67.9+/-9.9 years) with PAF (duration from onset of symptoms<24 h) secondary to hypertension. None had heart failure or any other ongoing inflammatory process. All patients received anticoagulation and intravenous amiodarone for cardioversion. High sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and tumour necrosis factor (TNF)-alpha were measured on admission and 48 h later. By 48 h from admission 61/75 patients (81.3%) regained sinus rhythm (cardioverted), whereas 14/75(18.7%) remained in AF (non-cardioverted). hsCRP, IL-6 and TNF-alpha serum levels on admission were similar between groups. hsCRP at 48 h was the most significant factor correlated with cardioversion outcome (OR: 0.06, 95% CI: 0.01-0.47, P=0.008). During a 1-year follow-up, AF recurred in 28/61(45.9%) patients. The strongest factor associated with AF recurrence was hsCRP at 48 h > or =2.27 mg l(-1) (hazard ratio: 6.2, 95% CI: 2.2-17.6, P=0.001). hsCRP at 48 h after admission correlates with cardioversion outcome and may predict long-term AF recurrence.
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PMID:Hypertension and paroxysmal atrial fibrillation: a novel predictive role of high sensitivity C-reactive protein in cardioversion and long-term recurrence. 2007 46

Several previous studies have suggested that n-3 polyunsaturated fatty acids (n-3 PUFA) can exert favourable effects in patients with heart failure, but the mechanisms involved are not fully understood. This study was designed to investigate the effects of n-3 PUFA on circulating inflammatory markers and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with heart failure. Seventy-six patients with heart failure were randomly assigned to receive 2 g/day of n-3 PUFA or placebo for 3 months. Treatment with n-3 PUFA significantly decreased plasma levels of tumour necrosis factor, interleukin-6, intercellular adhesion molecule 1 and NT-proBNP. Left ventricular ejection fraction showed a small, non-significant improvement. High-sensitivity C-reactive protein levels decreased significantly in smokers after n-3 PUFA treatment. Thus, n-3 PUFA can reduce levels of plasma inflammatory markers and NT-proBNP as biomarkers of risk stratification in patients with heart failure. n-3 PUFA may offer a novel therapy for heart failure.
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PMID:Effects of n-3 polyunsaturated fatty acid therapy on plasma inflammatory markers and N-terminal pro-brain natriuretic peptide in elderly patients with chronic heart failure. 2014 81

In the last decade, biologic agents, in particular anti-TNF agents such as infliximab, adalimumab, and certolizumab have substantially extended the therapeutic armamentarium of inflammatory bowel disease (IBD). Additional approaches include biologicals, such as natalizumab, that block leucocyte adhesion; those that target cytokines, such as interleukin-12/23 antibodies; or those that inhibit T-cell signaling, such as interleukin-6 receptor antibodies. However, these drugs have a number of contraindications and side effects, especially when used in combination with classical immunosuppressive agents or corticosteroids. Areas of concern include opportunistic infections, malignancies, and miscellaneous complications such as injection/infusion reactions and autoimmunity and contraindications, such as heart failure and acute infectious diseases. In this review, the indications of biologicals in IBD treatment are briefly reported, and the potential disadvantages of a more active therapeutic approach in IBD are discussed. We have learned in the last decade that anti-TNF-alpha therapy is an effective and relatively safe treatment option for selected patients that changes the natural course of severe IBD. However, despite these changed therapeutic paradigms and goals in IBD, clinicians should be aware that the powerful immunosuppressive capacity of biologicals necessitates a rigorous long-term safety follow-up.
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PMID:Adverse effects of biologics used for treating IBD. 2022 30


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