Tumor Necrosis Factor-α and Its Receptors 1 and 2

Schulz, Rainer; Heusch, Gerd

doi:10.1161/circulationaha.108.846105

Cited by 81 publications

(51 citation statements)

References 36 publications

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“…It is known that there is no detectable mRNA expression of pro-inflammatory cytokines in normal myocardial tissue, 37 but once cardiac injury sets in (such as with an MI), the intracardiac expression of IL-6, TNF-a and IFN-g mRNA expression possibly mediate the events of remodeling in the myocardium as reported earlier. [38][39][40][41][42] An increased expression of these cytokines may result in enhanced production of tissue repair molecules. Our results support this assumption, as myocardial mRNA expression of MMP-2, SDF-1 and TGF-b was significantly higher in chronic tobacco-exposed rats compared with tobacco-naïve rats with MI.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant N-acetyl cysteine reverses cigarette smoke-induced myocardial infarction by inhibiting inflammation and oxidative stress in a rat model

Khanna

Mehra

2012

Laboratory Investigation

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The contribution of chronic tobacco exposure in determining post-myocardial infarction (MI) left ventricular (LV) remodeling and possible therapeutic strategies has not been investigated systematically. In this small animal investigation, we demonstrate that chronic tobacco smoke exposure leading up to acute MI in rats is associated with greater histological extent of myocardial necrosis and consequent worse LV function. These findings are associated with increased transcriptomic expression of pro-inflammatory cytokines, tissue repair molecules and markers of oxidative stress in the myocardium. The results demonstrate that an N-acetyl cysteine (NAC) treatment significantly reduced tobacco-exposed induced infarct size and percent fractional shortening. A significantly increased LV end-systolic diameter was observed in tobacco-exposed sham compared to tobacco-naïve sham (4.92 ± 0.41 vs 3.45 ± 0.33; Po0.05), and tobacco-exposed MI compared to tobacco-naïve MI (8.24±0.3 vs 6.1±0.49; Po0.01) rats. Decreased intracardiac mRNA expression of the markers of inflammation, tissue repair and oxidative stress and circulating levels of pro-inflammatory cytokines accompanied these positive effects of NAC. The treatment of tobacco-exposed MI rats with NAC resulted in significantly increased levels of intracardiac mRNA expression of antioxidants, including superoxide dismutase, thioredoxin and nuclear factor-E2-related factor 2, as well as circulating levels of glutathione (7 ± 0.12 vs 10 ± 0.18; Pp0.001), where the levels were almost identical to the tobacco-naïve sham rats. These findings identify a novel post-infarction therapy for amelioration of the adverse effects of tobacco exposure on the infracted myocardium and advocate the use of dietary supplement antioxidants for habitual smokers to prevent and reverse cardiovascular adverse effects in the absence of successful achievement of cessation of smoking. Globally, tobacco smoke exposure remains a significant risk for the development of acute myocardial infarction (MI) irrespective of ethic or gender disparities. Exposure to tobacco smoke increases inflammation, oxidative stress 1-10 and decreases antioxidant expression. [11][12][13][14][15] Direct and indirect studies have demonstrated that oxidative stress from reactive oxygen species (ROS) generated through mitochondria, xanthine oxidase, and the NADPH oxidase system 16-21 is one of the important factors in the pathogenesis of myocardial ischemia. Decreased infarct size in superoxide dismutase (SOD)-producing transgenic mice suggests direct evidence for the role of involvement of ROS in MI. 22,23 In limited investigations, the use of antioxidants such as mercaptopropionyl glycine, edaravone and probucol have demonstrated varied effects on remodeling in animal models of MI, [24][25][26][27][28][29][30][31][32] with improvement in collagen content and histological changes. In this study, we sought to delineate the role of chronic tobacco smoke leading up to an acute MI by focusing on oxidative stress coupled with inflammat...

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Section: Discussionmentioning

confidence: 99%

Antioxidant N-acetyl cysteine reverses cigarette smoke-induced myocardial infarction by inhibiting inflammation and oxidative stress in a rat model

Khanna

Mehra

2012

Laboratory Investigation

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“…TNF-is released from mast cells and macrophages in the myocardial endothelium during acute MI, and from cardiomyocytes during persistent ischemia. The released TNF-contributes to ischemic and/or reperfusion injury and is believed to contribute to cardiac contractile dysfunction after MI via a local inflammatory reaction [31]. Surprisingly, low levels of TNF-may be beneficial and display a cardioprotective effect, reducing infarct size [31].…”

Section: Tnf-mentioning

confidence: 99%

“…The released TNF-contributes to ischemic and/or reperfusion injury and is believed to contribute to cardiac contractile dysfunction after MI via a local inflammatory reaction [31]. Surprisingly, low levels of TNF-may be beneficial and display a cardioprotective effect, reducing infarct size [31]. TNF-is also believed to play a role in the development of atherosclerosis by up-regulating cell surface receptors for advanced glycation end products that promote the release of inflammatory mediators in the endothelium [30].…”

Section: Tnf-mentioning

confidence: 99%

“…As a class, ARBs are known to have anti-inflammatory properties, which may contribute to their pharmacologic effects. Biomarker studies in hypertensive patients have demonstrated the effects of ARBs on inflammatory and other biomarkers [7,14], including CAP [15,16], hsCRP [14,[17][18][19], adiponectin [20], cystatin [21,22], HOMA-IR [23][24][25], procollagen [26][27][28], TNF- [29][30][31], and IL-6 [32][33][34].…”

Section: Introductionmentioning

confidence: 99%

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The Effects of Antihypertensive Agents in Metabolic Syndrome – Benefits Beyond Blood Pressure Control

Merchant¹,

Khan²

2012

Insulin Resistance

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“…The two TFNRs differ in their signal pathways with TNFR1 activating both apoptotic and protective signaling whereas TNFR2, although poorly studied, seem to convey prosurvival signaling only (Schulz and Heusch 2009). In a dose and time-dependent manner and function to which type of receptor is activated, TNF can be either protective or deleterious.…”

Section: Safe Pathwaymentioning

confidence: 99%

Cardiac Postconditioning: An Additional Therapy to Limit Cell Death Following Myocardial Infarction

Lecour¹,

Opie²,

Somers³

2012

Coronary Interventions

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Tumor Necrosis Factor-α and Its Receptors 1 and 2

Cited by 81 publications

References 36 publications

Antioxidant N-acetyl cysteine reverses cigarette smoke-induced myocardial infarction by inhibiting inflammation and oxidative stress in a rat model

Antioxidant N-acetyl cysteine reverses cigarette smoke-induced myocardial infarction by inhibiting inflammation and oxidative stress in a rat model

The Effects of Antihypertensive Agents in Metabolic Syndrome – Benefits Beyond Blood Pressure Control

Cardiac Postconditioning: An Additional Therapy to Limit Cell Death Following Myocardial Infarction

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