Tumor necrosis factor in the heart

Meldrum, Daniel R.

doi:10.1152/ajpregu.1998.274.3.r577

Cited by 553 publications

(620 citation statements)

References 286 publications

(340 reference statements)

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“…This cardiac inflammation is linked with decreased LV function, not only in diabetic cardiomyopathy, but also for example in myocardial infarction, pressure overload, and dilated cardiomyopathy [20][21][22]. Increased cytokines are one of the mechanisms leading to LV dysfunction in diabetes mellitus, as demonstrated by an inverse correlation between dP/dt max and TNF-α in diabetic animals in this study.…”

Section: Cardiac Inflammationsupporting

confidence: 58%

Inhibition of p38 mitogen-activated protein kinase attenuates left ventricular dysfunction by mediating pro-inflammatory cardiac cytokine levels in a mouse model of diabetes mellitus

et al. 2006

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Aims/hypothesis We investigated the effect of SB 203580, a pharmacological inhibitor of p38 mitogen-activated protein kinase (MAPK), on cardiac inflammation, cardiac fibrosis, and left ventricular function using an animal model of diabetic cardiomyopathy. Materials and methods Diabetes mellitus was induced by streptozotocin (50 mg/kg i.p. for 5 days) in 20 C57/BL6J mice. Diabetic mice were treated daily with the p38 MAPK inhibitor SB 203580 (1 mg/kg daily, n=10) or with placebo (n=10) and were compared to non-diabetic controls. Left ventricular function was measured by pressure-volume loops after 8 weeks of diabetes mellitus. The parameters for systolic function were the end systolic pressure-volume relationship (ESPVR) and the left ventricular end systolic pressure. The parameters for diastolic function were the left ventricular end diastolic pressure and the end diastolic pressure-volume relationship (EDPVR). Cardiac tissue was analysed by ELISA for the protein content of the cytokines TNF-α, IL6, IL1-β, and TGF-β1. Phosphorylation of MAPK p38 was analysed by western blot, and the total cardiac collagen content was analysed by Sirius red staining.

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Section: Cardiac Inflammationsupporting

confidence: 58%

Inhibition of p38 mitogen-activated protein kinase attenuates left ventricular dysfunction by mediating pro-inflammatory cardiac cytokine levels in a mouse model of diabetes mellitus

et al. 2006

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“…We found that, in the absence of extracellular Ca 2ϩ , cardiomyocytes maintained a normal rod-shaped morphology; however, the addition of extracellular Ca 2ϩ resulted in a loss of viability as indicated by rounding of the cells, which was markedly accelerated in cells with increased TRPC3 expression. In contrast, TRPC3 overexpression had no effect on the response of cardiomyocytes to TNF-␣, which induces apoptosis via a Ca 2ϩ -independent pathway by means of the TNF type-1 receptor and Fas activation (22) (Fig. 7).…”

Section: Discussionmentioning

confidence: 96%

Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes

Shan

Marchase²,

Chatham

2008

American Journal of Physiology-Cell Physiology

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Shan D, Marchase RB, Chatham JC. Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes. Am J Physiol Cell Physiol 294: C833-C841, 2008. First published January 9, 2008 doi:10.1152/ajpcell.00313.2007.-An increase in cytosolic Ca 2ϩ via a capacitative calcium entry (CCE)-mediated pathway, attributed to members of the transient receptor potential (TRP) superfamily, TRPC1 and TRPC3, has been reported to play an important role in regulating cardiomyocyte hypertrophy. Increased cytosolic Ca 2ϩ also plays a critical role in mediating cell death in response to ischemiareperfusion (I/R). Therefore, we tested the hypothesis that overexpression of TRPC3 in cardiomyocytes will increase sensitivity to I/R injury. Adult cardiomyocytes isolated from wild-type (WT) mice and from mice overexpressing TRPC3 in the heart were subjected to 90 min of ischemia and 3 h of reperfusion. After I/R, viability was 51 Ϯ 1% in WT mice and 42 Ϯ 5% in transgenic mice (P Ͻ 0.05). Apoptosis assessed by annexin V was significantly increased in the TRPC3 group compared with WT (32 Ϯ 1% vs. 21 Ϯ 3%; P Ͻ 0.05); however, there was no significant difference in necrosis between groups. Treatment of TRPC3 cells with the CCE inhibitor SKF-96365 (0.5 M) significantly improved cellular viability (54 Ϯ 4%) and decreased apoptosis (15 Ϯ 4%); in contrast, the L-type Ca 2ϩ channel inhibitor verapamil (10 M) had no effect. Calpain-mediated cleavage of ␣-fodrin was increased approximately threefold in the transgenic group following I/R compared with WT (P Ͻ 0.05); this was significantly attenuated by SKF-96365. The calpain inhibitor PD-150606 (25 M) attenuated the increase in both ␣-fodrin cleavage and apoptosis in the TPRC3 group. Increased TRPC3 expression also increased sensitivity to Ca 2ϩ overload stress, but it did not affect the response to TNF-␣-induced apoptosis. These results suggest that CCE mediated via TRPC may play a role in cardiomyocyte apoptosis following I/R due, at least in part, to increased calpain activation.

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“…Adiponectin belongs to an adipokine superfamily. Another adipokine, TNFα, is also expressed and secreted from cardiomyocytes [27]. Interestingly, the globular domain of adiponectin displays highly similar homo-trimeric three-dimensional structures to that of TNFα, even though they have unrelated amino-acid sequences [28].…”

Section: Discussionmentioning

confidence: 99%

Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor γ

Ding¹,

Qin²,

He³

et al. 2007

Journal of Molecular and Cellular Cardiology

127

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Adiponectin is a protein hormone involved in maintaining energy homeostasis in metabolically active tissues. It enhances glucose and lipid metabolism via activation of AMP-dependent kinase (AMPK) in skeletal muscle and liver. Energy homeostasis is vital for the heart to work as a pump. In this study, we investigated whether adiponectin and its receptors are expressed in adult ventricular cardiomyocytes. We observed adiponectin transcript and protein in cultured ventricular cardiomyocytes isolated from adult rat, by quantitative real-time PCR, ELISA assays, Western blots, and immunofluorescent staining. In addition, we detected adiponectin receptor (AdipoR1 and AdipoR2) expression in the heart. AdipoR1 was expressed in rat myocardium at a level of about 50% of that in skeletal muscle; whereas adipoR2 was expressed at a similar level to that in liver. Rosiglitazone, a Peroxisome proliferator activated receptor γ (PPARγ) activator, substantially elevated expression of adiponectin in cultured cardiomyocytes and its secretion into cultured media. Rosiglitazone also increased adipoR1 and adipoR2 expression in cardiomyocytes. Treatment of recombinant globular adiponectin in cultured cardiomyocytes increased fatty acid oxidation and glucose uptake via activation of AMPK, suggesting a role for adiponectin in cardiac energy metabolism. Together, these data establish the existence of a local cardiac-specific adiponectin system that is regulated by PPARγ. Moreover, these findings indicate a role for adiponectin on normal myocardial energy homeostasis, in part, through the activation of AMPK.

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Tumor necrosis factor in the heart

Cited by 553 publications

References 286 publications

Inhibition of p38 mitogen-activated protein kinase attenuates left ventricular dysfunction by mediating pro-inflammatory cardiac cytokine levels in a mouse model of diabetes mellitus

Inhibition of p38 mitogen-activated protein kinase attenuates left ventricular dysfunction by mediating pro-inflammatory cardiac cytokine levels in a mouse model of diabetes mellitus

Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes

Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor γ

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