Increased circulating cytokines inpatients with myocarditis andcardiomyopathy
01 Jan 2017-
TL;DR: In this paper, the potential role of cytokines in the pathogenesis of cardiomyopathy and myocarditis was elucidated, and experimental studies showed that certain cytokines depress myocardial
Abstract: Objectives-To elucidate thepotential roleofcytokines inthepathogenesis of cardiomyopathy andmyocarditis. Background-Experimental studies show thatcertain cytokines depress myocardial
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TL;DR: This review focuses only on permanent modifications in relation to clinical dysfunction in cardiac remodeling secondary to myocardial infarction and/or arterial hypertension and includes a special section on the senescent heart, since CR is mainly a disease of the elderly.
Abstract: Swynghedauw, Bernard. Molecular Mechanisms of Myocardial Remodeling. Physiol. Rev. 79: 215–262, 1999. — “Remodeling” implies changes that result in rearrangement of normally existing structures. Th...
1,489 citations
TL;DR: Circulating levels of proinflammatory cytokines increase in patients as their functional heart failure classification deteriorates, and activation of the neurohumoral axis is unlikely to completely explain the elaboration of pro inflammatory cytokines in heart failure.
1,207 citations
TL;DR: TNFR1 and TNFR2 receptor protein levels, as measured by ELISA, were decreased 60% in DCM and IHD patients compared with nonfailing hearts, to determine a potential mechanism for the decrease in TNF receptor expression.
Abstract: Background Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine that produces negative inotropic effects in the heart. Recently, elevated levels of TNF-α have been reported in patients with advanced congestive heart failure. Although TNF-α is thought to exert its deleterious effects by binding to two cell surface receptors, TNFR1 and TNFR2, the level of expression and regulation of TNF receptors in the heart in cardiac disease states is not known. Methods and Results We examined mRNA and protein levels for TNFR1, TNFR2, and TNF-α in explanted hearts from organ donors as well as in patients with end-stage dilated cardiomyopathy (DCM) and ischemic heart disease (IHD). Northern blot analysis revealed that mRNA for TNFR1 and TNFR2 was present in nonfailing, DCM, and IHD hearts. TNFR1 and TNFR2 receptor protein levels, as measured by ELISA, were decreased 60% in DCM and IHD patients compared with nonfailing hearts (P<.005). To determine a potential mechanism for the decrease in TNF receptor expression...
961 citations
TL;DR: In conclusion, the mouse overexpressing TNF-alpha recapitulated the phenotype of congestive heart failure and provides a novel model to elucidate the role of this cytokine in the development of congestives heart failure.
Abstract: The failing human heart expresses tumor necrosis factor-α (TNF-α). However, its pathophysiological significance is not clear. We previously reported that robust overexpression of TNF-α in the murine heart causes lethal myocarditis. In this study, we modified the transgene to reduce the production of TNF-α by preserving the destabilizing sequence in TNF-α cDNA. Expression was driven by the murine α-myosin heavy chain promoter. Use of this modified construct allowed us to establish a murine transgenic line (TG). TG offspring were examined at 6, 12, and 24 weeks. All showed a significantly higher heart weight–to–body weight ratio. Northern blot analysis confirmed the expression of transgene in the heart, and enzyme-linked immunosorbent assay demonstrated the presence of TNF-α protein. The TG heart demonstrated a mild, diffuse, lymphohistiocytic interstitial inflammatory infiltrate. Cardiomyocyte necrosis and apoptosis were present but not abundant. Magnetic resonance imaging showed that the TG heart...
842 citations
TL;DR: Anthracyclines are clearly an important independent risk factor leading to both early and delayed congestive heart failure in survivors of cancer, and late-onset cardiomyopathy depends on the cumulative dose of the drug.
Abstract: Purpose: To review the current understanding of the clinical significance, detection, pathogenesis, and prevention of anthracycline-induced cardiotoxicity. Data Sources: A MEDLINE search of the Eng...
702 citations
References
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TL;DR: It is indicated that circulating levels of tumor necrosis factor are increased in cachectic patients with chronic heart failure and that this elevation is associated with the marked activation of the renin-angiotensin system seen in patients with end-stage cardiac disease.
Abstract: Background and Methods. Although cachexia often accompanies advanced heart failure, little is known about the causes of the cachectic state. To assess the potential role of tumor necrosis factor in the pathogenesis of cardiac cachexia, we measured serum levels of the factor in 33 patients with chronic heart failure, 33 age-matched healthy controls, and 9 patients with chronic renal failure. Results. Mean (±SEM) serum levels of tumor necrosis factor were higher in the patients with heart failure (115±25 U per milliliter) than in the healthy controls (9±3 U per milliliter; P 2 SD above the mean value for the control group), whereas the remaining 14 patients had serum levels of tumor necrosis factor below this level. The patients with high levels of tumor necrosis factor were more cachectic than those with low levels (82±3 vs. 95±6 percent of ideal body weight, respectively; P...
2,528 citations
TL;DR: The findings demonstrate that the direct negative inotropic effect of cytokines is mediated through a myocardial nitric oxide synthase, and the regulation of pro-inflammatory cytokines and myocardia nitricoxide synthase may provide new therapeutic strategies for the treatment of cardiac disease.
Abstract: The direct effects of pro-inflammatory cytokines on the contractility of mammalian heart were studied. Tumor necrosis factor alpha, interleukin-6, and interleukin-2 inhibited contractility of isolated hamster papillary muscles in a concentration-dependent, reversible manner. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) blocked these negative inotropic effects. L-Arginine reversed the inhibition by L-NMMA. Removal of the endocardial endothelium did not alter these responses. These findings demonstrate that the direct negative inotropic effect of cytokines is mediated through a myocardial nitric oxide synthase. The regulation of pro-inflammatory cytokines and myocardial nitric oxide synthase may provide new therapeutic strategies for the treatment of cardiac disease.
1,641 citations
TL;DR: Identification of two unique mutations within cardiac MHC genes in all individuals with FHC from two unrelated families demonstrates that defects in the cardiac M HC genes can cause this disease.
1,264 citations
Journal Article•
1,235 citations
TL;DR: It is suggested that the precise definition of the disease-causing mutation can provide important prognostic information about affected members in families with hypertrophic cardiomyopathy.
Abstract: Background Familial hypertrophic cardiomyopathy is characterized by a variable degree of myocardial hypertrophy and a wide range of symptoms. Different mutations in the β cardiac myosin heavy-chain gene have been identified in three affected families. However, neither the proportion of cases attributable to myosin mutations nor the effects of different mutations on clinical outcome are known. Methods Using a ribonuclease protection assay, we screened the β cardiac myosin heavy-chain genes of probands from 25 unrelated families with familial hypertrophic cardiomyopathy; this assay is a sensitive method for detecting the presence and location of mutations. We further defined the mutations by analyzing their nucleotide sequences. The clinical features of the disease were compared in families with various myosin mutations. Results Seven mutations in the β cardiac myosin heavy-chain gene were identified in 12 of the 25 families. All were missense mutations (i.e., causing the substitution of a single a...
686 citations