Detrimental effect of fractalkine on myocardial ischaemia and heart failure

Wang, Xuan; Liao, Yulin; Chen, Baihe; Huang, Qiaobing; Xu, Dingli; Liu, Yili; Bin, Jianping; Kitakaze, Masafumi

doi:10.1093/cvr/cvr221

Cited by 71 publications

(91 citation statements)

References 30 publications

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“…Moreover, the observation of high embryonic mortality and organ defects, including cardiac ventricular septum defects, in CXC chemokine receptor 4 knockout mice indicates a crucial and direct dependence on chemokines in the development and function of the myocardium [81]. Furthermore, we have shown increased CX3C chemokine ligand (CX3CL)1 production in both experimental and clinical HF [82], and very recently, Xuan et al [83] showed that neutralizing CX3CL1 antibody treatment improved HF induced by MI or pressure overload. Other recent studies have also suggested a direct role for chemokines in ECM remodeling.…”

Section: Immunomodulating Therapy Ii: New Therapeutic Targetsmentioning

confidence: 99%

Inflammatory Cytokines in Heart Failure: Mediators and Markers

Gullestad

Ueland²,

Vinge³

et al. 2012

Cardiology

311

236

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Evidence from both experimental and clinical trials indicates that inflammatory mediators are of importance in the pathogenesis of chronic heart failure (HF) contributing to cardiac remodeling and peripheral vascular disturbances. Several studies have shown raised levels of inflammatory cytokines such as tumor necrosis factor (TNF)α, interleukin (IL)-1β and IL-6 in HF patients in plasma and circulating leukocytes, as well as in the failing myocardium itself. There is strong evidence that these mediators are involved in processes leading to cardiac remodeling such as hypertrophy, fibrosis and apoptosis. Some of these cytokines can also give useful prognostic information as reliable biomarkers in this disorder. In general, immunomodulating treatments have, with a few exceptions, been neutral or even harmful. However, the negative results of anti-TNF studies, for instance, do not necessarily argue against the ‘cytokine hypothesis’. These studies just underscore the challenges in developing treatment modalities that can modulate the cytokine network in HF patients and result in beneficial net effects. Future studies should identify the crucial actors and their mechanisms of action in the immunopathogenesis of chronic HF and, in particular, clarify the balance between adaptive and maladaptive effects of these molecules. Such studies are a prerequisite for the development of new treatment strategies that target inflammatory and immunopathogenic mechanisms in HF. In this review article, these issues are thoroughly discussed, and we also argue for the possibility of future therapeutic targets such as mediators in innate immunity, chemokines and mediators in matrix remodeling.

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Section: Immunomodulating Therapy Ii: New Therapeutic Targetsmentioning

confidence: 99%

Inflammatory Cytokines in Heart Failure: Mediators and Markers

Gullestad

Ueland²,

Vinge³

et al. 2012

Cardiology

311

236

View full text Add to dashboard Cite

show abstract

“…culture of ventricular cardiomyocytes and fibroblast cells were performed as described elsewhere [30]. Subsequently, primary cardiomyocytes and passage 1 fibroblasts were exposed to histamine, amthamine dihydrobromide (AD, a selective H2R agonist) or famotidine (a selective H2R antagonist -all were purchased from Sigma-Aldrich) for the indicated dose and time as described in the corresponding Figure legend, and then the related gene and protein expression levels, as well as mitochondrial permeability and apoptosis, were analysed.…”

Section: Cell Culturementioning

confidence: 99%

Disruption of histamine H2 receptor slows heart failure progression through reducing myocardial apoptosis and fibrosis

Zeng

Shen

et al. 2014

Clinical Science

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Histamine H2 receptor (H2R) blockade has been reported to be beneficial for patients with chronic heart failure (CHF), but the mechanisms involved are not entirely clear. In the present study, we assessed the influences of H2R disruption on left ventricular (LV) dysfunction and the mechanisms involved in mitochondrial dysfunction and calcineurin-mediated myocardial fibrosis. H2R-knockout mice and their wild-type littermates were subjected to transverse aortic constriction (TAC) or sham surgery. The influences of H2R activation or inactivation on mitochondrial function, apoptosis and fibrosis were evaluated in cultured neonatal rat cardiomyocytes and fibroblasts as well as in murine hearts. After 4 weeks, H2R-knockout mice had higher echocardiographic LV fractional shortening, a larger contractility index, a significantly lower LV end-diastolic pressure, and more importantly, markedly lower pulmonary congestion compared with the wild-type mice. Similar results were obtained in wild-type TAC mice treated with H2R blocker famotidine. Histological examinations showed a lower degree of cardiac fibrosis and apoptosis in H2R-knockout mice. H2R activation increased mitochondrial permeability and induced cell apoptosis in cultured cardiomyocytes, and also enhanced the protein expression of calcineurin, nuclear factor of activated T-cell and fibronectin in fibroblasts rather than in cardiomyocytes. These findings indicate that a lack of H2R generates resistance towards heart failure and the process is associated with the inhibition of cardiac fibrosis and apoptosis, adding to the rationale for using H2R blockers to treat patients with CHF.

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“…10 Moreover, FKN augments myocardial injury and accelerates the progress of heart failure with activation of MAPK/ERK signaling through the G protein-coupled chemokine receptor CX3CR1. 24 The activation of MAPK pathways plays a key role in the progression to cardiac hypertrophy and heart failure. 3 Intriguingly, ings implied regulatory roles of ACE2 in oxidative stress, and the CTGF-FKN-ERK and MMP signaling pathways.…”

Section: Treatment With Rhace2 Suppressed Angii-mediated Oxidative Stmentioning

confidence: 99%

Loss of Angiotensin-Converting Enzyme 2 Exacerbates Myocardial Injury via Activation of the CTGF-Fractalkine Signaling Pathway

Song

Zhang

Zhong

et al. 2013

Circ J

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Detrimental effect of fractalkine on myocardial ischaemia and heart failure

Abstract: FKN promotes myocardial injury and accelerates the progress of heart failure, which is associated with the activation of MAPKs.

Cited by 71 publications

References 30 publications

Inflammatory Cytokines in Heart Failure: Mediators and Markers

Inflammatory Cytokines in Heart Failure: Mediators and Markers

Disruption of histamine H2 receptor slows heart failure progression through reducing myocardial apoptosis and fibrosis

Loss of Angiotensin-Converting Enzyme 2 Exacerbates Myocardial Injury via Activation of the CTGF-Fractalkine Signaling Pathway

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