Endotoxin and Cytokines Induce Direct Cardiodepressive Effects in Mammalian Cardiomyocytes via Induction of Nitric Oxide Synthase

Stein, Birgitt; Frank, Petra; Schmitz, Wilhelm; Scholz, Hasso; Thoenes, Martin

doi:10.1006/jmcc.1996.0153

Cited by 151 publications

(110 citation statements)

References 2 publications

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“…Furthermore, the contractile abnormalities seen in this model were not restored in the present of NOS inhibitors, L-NMMA and L-nitroarginine (L-NA) [104]. These findings were supported by similar finding in two other studies following treatment with LPS in adult guinea pig cardiac myocytes and isolated perfused rat hearts [105,106].…”

Section: Effects Of No and Cytokines On Contraction In Isolated Cardisupporting

confidence: 89%

The complex role of iNOS in acutely rejecting cardiac transplants

Pieper

Roza

2008

Free Radical Biology and Medicine

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This review summarizes the evidence for a detrimental role of nitric oxide (NO) derived from inducible NO synthase (iNOS) and/or reactive nitrogen species such as peroxynitrite in acutelyrejecting cardiac transplants. In chronic cardiac transplant rejection, iNOS may have an opposing beneficial component. The purpose of this review is primarily to address issues related to acute rejection which is a recognized risk factor for chronic rejection. The evidence for a detrimental role is based upon strategies involving non-selective NOS inhibitors, NO neutralizers, selective iNOS inhibitors and iNOS gene deletion in rodent models of cardiac rejection. The review is discussed in the context of the impact on various components including graft survival, histological rejection and cardiac function which may contribute in toto to the process of graft rejection. Possible limitations of each strategy are discussed in order to understand better the variance in published findings including issues related to the potential importance of cell localization of iNOS expression. Finally, the concept of a dual role of NO and its down-stream product, peroxynitrite, in rejection vs. immune regulation is discussed.

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Section: Effects Of No and Cytokines On Contraction In Isolated Cardisupporting

confidence: 89%

The complex role of iNOS in acutely rejecting cardiac transplants

Pieper

Roza

2008

Free Radical Biology and Medicine

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“…Prolonged (>18 hour) exposure to LPS, TNF-α, or IL-1β decreased contractility of guinea pig cardiomyocytes, while increasing cGMP content and NOS 2 levels [8]. All of these effects were abolished when the steroid dexamethasone was added to culture.…”

Section: Nitric Oxidementioning

confidence: 95%

“…Several types of nucleated cells produce and locally release these proteins in response to surgical, traumatic, ischemic or septic insults [7]. Studies performed on rodent models of sepsis show significant decreases in measures of contractility in cardiomyocytes exposed in vitro to TNF-α, IL-1β [8], and IL-6 [9]. Accordingly, patients with sepsis demonstrate higher levels of interleukins and complement components in their bloodstream [2].…”

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confidence: 99%

Sepsis-induced cardiomyopathy: a review of pathophysiologic mechanisms

2010

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“…9,10 Induction of iNOS in cardiomyocytes was likewise demonstrated in an animal model in which septic shock was produced by administration of lipopolysaccharide (LPS) or endotoxin derived from gram-negative bacterial membranes. 11,12 The suppressor of cytokine signaling (SOCS) family is a recently identified group of proteins (SOCS1 to SOCS7 and cytokine-inducible SH2-containing protein) that function in a negative feedback loop that regulates signaling mediated by cytokine receptors via the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway. [13][14][15] SOCS proteins appear to use several mechanisms to inhibit cytokine signaling.…”

mentioning

confidence: 99%

SOCS1/JAB Likely Mediates the Protective Effect of Cardiotrophin-1 Against Lipopolysaccharide-Induced Left Ventricular Dysfunction In Vivo

Tanimoto¹,

Saito²,

Hamanaka³

et al. 2005

Circ J

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roinflammatory cytokines are involved in the pathogenesis of various heart diseases, such as septic shock, myocarditis, some cases of dilated cardiomyopathy, ischemic heart disease and cardiac hypertrophy. [1][2][3][4][5][6][7] The effects of some cytokines, which act in an autocrine or paracrine manner, on the heart have been extensively studied. Contributing to the profound cardiocirculatory abnormalities in septic shock is myocardial depression, which some evidence suggests can be attributed to circulating inflammatory cytokines such as tumor necrosis factor (TNF)-, interleukin (IL)-1 and interferon (IFN)-. 8 These mediators activate nuclear factor (NF)-B in cardiomyocytes, which in turn leads to upregulation of inducible nitric oxide synthase (iNOS) expression, resulting in acute left ventricular (LV) dysfunction caused by the negative inotropic effect of nitric oxide (NO). 9,10 Induction of iNOS in cardiomyocytes was likewise demonstrated in an animal model in which septic shock was produced by administration of lipopolysaccharide (LPS) or endotoxin derived from gram-negative bacterial membranes. 11,12 The suppressor of cytokine signaling (SOCS) family is a recently identified group of proteins (SOCS1 to SOCS7 and cytokine-inducible SH2-containing protein) that function in a negative feedback loop that regulates signaling mediated by cytokine receptors via the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway. [13][14][15] SOCS proteins appear to use several mechanisms to inhibit cytokine signaling. 16 For instance, SOCS1/ JAB (JAK binding protein), which is activated by phosphorylated STAT1 and STAT3, binds directly to the kinase domain of JAK1 and JAK2, thereby inhibiting STAT signal transduction. SOCS1 also suppresses LPS signal transduction through one of the Toll-like receptors (TLRs), TLR4, via which LPS triggers innate immune responses. 17,18 In addition, SOCS1 reportedly inhibits signaling by mediators other than JAK-STAT, including TNF-, insulin and Vav. [19][20][21][22] Although the SOCS1 target molecule in TLR4 signaling has not yet been identified, collectively the available data suggest that induction of SOCS1 could play a protective role during septic shock by modulating the cardiovascular response.We recently reported that intravenous injection of cardiotrophin-1 (CT-1), a cytokine in the IL-6 family, into Wistar rats induces phosphorylation of STAT3 and expression of SOCS1 and SOCS3 in various tissues. 23 In addition, injection of CT-1 induced resistance to a second CT-1 injection; that is, it lead to attenuation of the STAT3 phosphorylation, iNOS mRNA expression and blood pressure reduction seen otherwise. In the present report we show that induction of Background Suppressor of cytokine signaling 1 (SOCS1) is a negative regulator of cytokine signaling whose expression is induced in the rat heart by cardiotrophin-1 (CT-1). Sepsis-induced myocardial depression results from the expression of inducible nitric oxide synthase (iNOS) evoked by inflammatory cytoki...

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Endotoxin and Cytokines Induce Direct Cardiodepressive Effects in Mammalian Cardiomyocytes via Induction of Nitric Oxide Synthase

Cited by 151 publications

References 2 publications

The complex role of iNOS in acutely rejecting cardiac transplants

The complex role of iNOS in acutely rejecting cardiac transplants

Sepsis-induced cardiomyopathy: a review of pathophysiologic mechanisms

SOCS1/JAB Likely Mediates the Protective Effect of Cardiotrophin-1 Against Lipopolysaccharide-Induced Left Ventricular Dysfunction In Vivo

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