Human cardiomyocyte hypertrophy induced in vitro by gp130 stimulation

Ancey, Cécile; Menet, Emmanuelle; Corbi, Pierre; Fredj, Sandra; Garcia, Martine; Rücker‐Martin, Catherine; Bescond, Jocelyn; Morel, Franck; Wijdenes, John; Lecron, Jean‐Claude; Potreau, Daniel

doi:10.1016/s0008-6363(03)00346-8

Cited by 56 publications

(41 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several groups, including our own, have shown that IL-6 is increased in cocultures of cardiac myocytes and fibroblasts (5,19,20,33). Studies have also examined the role and function of IL-6 in cardiac myocytes, with data suggesting regulatory roles in hypertrophy and atrial natriuretic peptide expression (1,2,33,47). Despite these suggested roles of IL-6, little has been explored in terms of the role of IL-6 on fibroblast-myocyte interactions.…”

Section: Il-6-loss Causes Ventricular Dysfunction and Increases Periomentioning

confidence: 99%

“…Moreover, studies in rats have demonstrated that constant IL-6/sIL-6R␣ stimulation can reduce infarct size and protect against myocyte apoptosis (35). Previous studies have also demonstrated that IL-6 plays an important role in cardiac myocyte function and gene expression (2,5,15,19,33,47,50,51). However, despite all of these studies, the functional effects of IL-6 loss on cardiac fibroblast-myocyte interactions remain largely unknown.…”

mentioning

confidence: 99%

See 1 more Smart Citation

IL-6 loss causes ventricular dysfunction, fibrosis, reduced capillary density, and dramatically alters the cell populations of the developing and adult heart

Banerjee¹,

Fuseler²,

Intwala³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

106

View full text Add to dashboard Cite

Interleukin-6 (IL-6) is a pleiotropic cytokine responsible for many different processes including the regulation of cell growth, apoptosis, differentiation, and survival in various cell types and organs, including the heart. Recent studies have indicated that IL-6 is a critical component in the cell-cell communication between myocytes and cardiac fibroblasts. In this study, we examined the effects of IL-6 deficiency on the cardiac cell populations, cardiac function, and interactions between the cells of the heart, specifically cardiac fibroblasts and myocytes. To examine the effects of IL-6 loss on cardiac function, we used the IL-6 −/− mouse. IL-6 deficiency caused severe cardiac dilatation, increased accumulation of interstitial collagen, and altered expression of the adhesion protein periostin. In addition, flow cytometric analyses demonstrated dramatic alterations in the cardiac cell populations of IL-6 −/− mice compared with wild-type littermates. We observed a marked increase in the cardiac fibroblast population in IL-6 −/− mice, whereas a concomitant decrease was observed in the other cardiac cell populations examined. Moreover, we observed increased cell proliferation and apoptosis in the developing IL-6 −/− heart. Additionally, we observed a significant decrease in the capillary density of IL-6 −/− hearts. To elucidate the role of IL-6 in the interactions between cardiac fibroblasts and myocytes, we performed in vitro studies and demonstrated that IL-6 deficiency attenuated the activation of the STAT3 pathway and VEGF production. Taken together, these data demonstrate that a loss of IL-6 causes cardiac dysfunction by shifting the cardiac cell populations, altering the extracellular matrix, and disrupting critical cell-cell interactions.

show abstract

Section: Il-6-loss Causes Ventricular Dysfunction and Increases Periomentioning

confidence: 99%

mentioning

confidence: 99%

IL-6 loss causes ventricular dysfunction, fibrosis, reduced capillary density, and dramatically alters the cell populations of the developing and adult heart

Banerjee¹,

Fuseler²,

Intwala³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

106

View full text Add to dashboard Cite

show abstract

“…IL-6 is produced by both cardiac fibroblasts and myocytes in the human heart [1,2] and exerts direct influences on cardiomyocytes and cardiac fibroblasts, respectively. In that, IL-6 is known to reduce cardiomyocyte contractility in vitro, partly via induction of iNOS expression and by decreasing intracellular Ca 2+ transients, most probably due to the downregulation of sarcoplasmic reticulum Ca 2+ ATPase (SERCA2) in cardiomyocytes [152].…”

Section: Interleukin-6 and Its Potential Role In The Heartmentioning

confidence: 99%

“…The LIF receptor and its ligand are also abundantly expressed in postnatal murine cardiomyocytes [2,77] and in vitro data show that LIF confers both hypertrophic and cytoprotective responses in adult cardiomyocytes [154]. LIF stimulation increases cardiomyocyte growth and promotes a fetal gene expression pattern (upregulated c-fos, β-MHC and ANF) [77,92].…”

Section: Leukemia Inhibitory Factor and Its Potential Role In The Heartmentioning

confidence: 99%

Survival pathways in hypertrophy and heart failure: The gp130-STAT3 axis

2007

View full text Add to dashboard Cite

■ Abstract Circulating levels of interleukin (IL)-6 and related cytokines are elevated in patients with congestive heart failure and after myocardial infarction. Serum IL-6 concentrations are related to decreasing functional status of these patients and provide important prognostic information. Moreover, in the failing human heart, multiple components of the IL-6-glycoprotein (gp)130 receptor system are impaired, implicating an important role of this system in cardiac pathophysiology.Experimental studies have shown that the common receptor subunit of IL-6 cytokines is phosphorylated in response to pressure overload and myocardial infarction and that it subsequently activates at least three different downstream signaling pathways, the signal transducers and activators of transcription 1 and 3 (STAT1/3), the Src-homology tyrosine phosphatase 2 (SHP2)-Ras-ERK, and the PI3K-Akt system. Gp130 receptor mediated signaling promotes cardiomyocyte survival, induces hypertrophy, modulates cardiac extracellular matrix and cardiac function. In this regard, the gp130 receptor system and its main downstream mediator STAT3 play a key role in cardioprotection.This review summarizes the current knowledge of IL-6 cytokines, gp130 receptor and STAT3 signaling in the heart exposed to physiological (aging, pregnancy) and pathophysiological stress (ischemia, pressure overload, inflammation and cardiotoxic agents) with a special focus on the potential role of individual IL-6 cytokines.

show abstract

“…10,[13][14][15] However, no studies to date have shown that IL-6 itself can cause vascular or cardiac hypertrophy either in vitro or in vivo. In addition, whether Ang II acting via IL-6 can activate STAT3 and gp130 signaling is unknown.…”

mentioning

confidence: 99%

Classic Interleukin-6 Receptor Signaling and Interleukin-6 trans-Signaling Differentially Control Angiotensin II-Dependent Hypertension, Cardiac Signal Transducer and Activator of Transcription-3 Activation, and Vascular Hypertrophy in Vivo

Coles

Fielding

Rose-John

et al. 2007

The American Journal of Pathology

119

View full text Add to dashboard Cite

Interleukin (IL)-6 acts via a receptor complex consisting of the cognate IL-6 receptor (IL-6R) or the soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (gp130).Here, we investigated the role of these IL-6R components in hypertension and vascular hypertrophy in mice. Angiotensin (Ang) II (1.1 mg/kg/day) caused hypertension and cardiac/aortic hypertrophy in wildtype, but not IL-6 ؊/؊ , mice throughout 7 days. A recombinant dimeric soluble gp130 (sgp130Fc; 50 to 100 g, i.p.) blocked Ang II hypertension but not hypertrophy in wild-type mice. Cognate IL-6R was detected in aortic smooth muscle, but its levels and those of plasma sIL-6R were ϳ50% decreased in IL-6 ؊/؊ mice. Ang II infusion activated signal transducer and activator of transcription-3 in heart of WT and decreased Ang II receptor 1 (ATR1) expression in aorta. Both responses were unaffected by sgp130Fc and absent in IL-6 ؊/؊ mice. In summary, we show that IL-6 trans-signaling is required for Ang II-dependent hypertension, but that hypertrophy, down-regulation of AT1R, and cardiac signal transducer and activator of transcription-3 activation are mediated via cognate IL-6R. These data show that IL-6 responses in a single disease context are governed by both modes of IL-6 signaling, with each pathway eliciting different outcomes. Inhibition of IL-6 signaling is suggested as a potential therapy for hypertension and cardiac hypertrophy. There is emerging evidence for a role of interleukin (IL)-6 and its related cytokines in angiotensin (Ang) II-dependent vascular dysfunction. Plasma levels of IL-6 are strongly associated with hypertension in humans and can be decreased by administration of Ang II receptor antagonists.

show abstract

Human cardiomyocyte hypertrophy induced in vitro by gp130 stimulation

Abstract: These results demonstrate that gp130 activation in human cardiac cells leads to cardiomyocyte hypertrophy. We discuss several hypotheses on the role of IL-6-type cytokines on cardiomyocyte functions.

Cited by 56 publications

References 35 publications

IL-6 loss causes ventricular dysfunction, fibrosis, reduced capillary density, and dramatically alters the cell populations of the developing and adult heart

IL-6 loss causes ventricular dysfunction, fibrosis, reduced capillary density, and dramatically alters the cell populations of the developing and adult heart

Survival pathways in hypertrophy and heart failure: The gp130-STAT3 axis

Classic Interleukin-6 Receptor Signaling and Interleukin-6 trans-Signaling Differentially Control Angiotensin II-Dependent Hypertension, Cardiac Signal Transducer and Activator of Transcription-3 Activation, and Vascular Hypertrophy in Vivo

Contact Info

Product

Resources

About