Activated toll-like receptor 4 in monocytes is associated with heart failure after acute myocardial infarction

Satoh, Mamoru; Shimoda, Yudai; Maesawa, Chihaya; Akatsu, Tomonari; Ishikawa, Yuh; Minami, Yoshitaka; Hiramori, Katsuhiko; Nakamura, Motoyuki

doi:10.1016/j.ijcard.2005.06.023

Cited by 117 publications

(104 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, several experimental studies in models of LV hypertrophy, ischemia/reperfusion injury, and sepsis provide further evidence for a relevance of this receptor in the development of cardiovascular diseases. (9, 16 -18) Studies in humans showed a correlation between TLR4 expression and myocardial ischemia, suggesting that this receptor might also play a clinical role (19,20).…”

Section: Yocardial Infarction (Mi)mentioning

confidence: 99%

Toll-Like Receptor-4 Modulates Survival by Induction of Left Ventricular Remodeling after Myocardial Infarction in Mice

Riad

Jäger

Sobirey

et al. 2008

The Journal of Immunology

114

View full text Add to dashboard Cite

Left ventricular (LV) remodeling is known to contribute to morbidity and mortality after myocardial infarction (MI). Because LV remodeling is strongly associated with an inflammatory response, we investigated whether or not TLR-4 influences LV remodeling and survival in a mice model of MI. Six days after MI induction, TLR4 knockout (KO)-MI mice showed improved LV function 32 and reduced LV remodeling as indexed by reduced levels of atrial natriuretic factor and total collagen as well as by a reduced heart weight to body weight ratio when compared with WT-MI mice. This was associated with a reduction of protein levels of the intracellular TLR4 adapter protein MyD88 and enhanced protein expression of the anti-hypertrophic JNK in KO-MI mice when compared with wild-type (WT)-MI mice. In contrast, protein activation of the pro-hypertrophic kinases protein kinase Cδ and p42/44 were not regulated in KO-MI mice when compared with WT-MI mice. Improved LV function, reduced cardiac remodeling, and suppressed intracellular TLR4 signaling in KO-MI mice were associated with significantly improved survival compared with WT-MI mice (62 vs 23%; p < 0.0001). TLR4 deficiency led to improved survival after MI mediated by attenuated left ventricular remodeling.

show abstract

Section: Yocardial Infarction (Mi)mentioning

confidence: 99%

Toll-Like Receptor-4 Modulates Survival by Induction of Left Ventricular Remodeling after Myocardial Infarction in Mice

Riad

Jäger

Sobirey

et al. 2008

The Journal of Immunology

114

View full text Add to dashboard Cite

show abstract

“…In addition to these static markers of inflammatory activity, we also analyzed the functional basis for altered inflammatory response by measuring monocyte intracellular proinflammatory cytokine production following ligation of Toll-like receptor 4 (TLR4) with lipopolysaccharide (LPS). TLRs mediate innate immune responses to common pathogens, and aberrant TLR activity has been linked to other inflammatory diseases, such as rheumatoid arthritis (27), Crohn's disease (27), and heart failure (28). We also evaluated another potential explanation for increased inflammatory cytokine production by assessing variations in the prevalence of cytokine producer cells, such as activated T lymphocytes, monocytes, or myeloid dendritic cells (29 -31).…”

mentioning

confidence: 99%

Inflammatory Biomarkers for Persistent Fatigue in Breast Cancer Survivors

Collado-Hidalgo¹,

Bower

Ganz

et al. 2006

Clinical Cancer Research

347

264

View full text Add to dashboard Cite

Purpose: This study seeks to define immunologic and inflammatory variables associated with persistent post-treatment fatigue in breast cancer survivors. Experimental Design: Leukocyte subsets, plasma inflammatory markers, and ex vivo proinflammatory cytokine production were assessed in 50 fatigued and nonfatigued breast cancer survivors recruited z2 years after successful primary therapy. Multivariate statistical analyses were used to define a composite immunologic biomarker of fatigue risk. Results: Fatigued breast cancer survivors were distinguished from nonfatigued survivors by increased ex vivo monocyte production of interleukin (IL)-6 and tumor necrosis factor-a following lipopolysaccharide stimulation, elevated plasma IL-1ra and soluble IL-6 receptor (sIL-6R/CD126), decreased monocyte cell-surface IL-6R, and decreased frequencies of activated T lymphocytes and myeloid dendritic cells in peripheral blood (all P < 0.05). An inverse correlation between sIL-6R and cell-surface IL-6R was consistent with inflammation-mediated shedding of IL-6R, and in vitro studies confirmed that proinflammatory cytokines induced such shedding. Multivariate linear discriminant function analysis identified two immunologic markers, the ratio of sIL-6R to monocyte-associated IL-6R and decreased circulating CD69 + T lymphocytes, as highly diagnostic of fatigue (P = 0.0005), with cross-validation estimates indicating 87% classification accuracy (sensitivity = 0.83; specificity = 0.83). Conclusion: These results extend links between fatigue and inflammatory markers to show a functional alteration in proinflammatory cytokine response to lipopolysaccharide and define a prognostic biomarker of behavioral fatigue.

show abstract

“…Although the healthy control group was small these data seem to indicate that TLR responsiveness could be different between diseased and non-diseased individuals. This notion is backed up by other reports showing that TLR4 mediated release of pro-inflammatory cytokines is higher in unstable angina or acute myocardial infarction patients than in patients with stable angina or healthy controls [9,11,15]. Responsiveness to TLR ligands has been assumed to be correlated with surface expression of the corresponding receptor.…”

Section: Al In This Issuementioning

confidence: 92%

“…Responsiveness to TLR ligands has been assumed to be correlated with surface expression of the corresponding receptor. The expression of TLR4 on monocytes has been shown to correlate to TNFα and IL-6 release after LPS stimulation [11]. Also, surface expression of TLR2 and TLR4 on circulating monocytes has been shown to be increased in acute myocardial infarction and unstable angina patients compared to healthy control patients [9,10].…”

Section: Al In This Issuementioning

confidence: 99%

“…Polymorphisms in the TLR4 gene have also been suggested to be associated with cardiovascular disease [2]. Surface expression of TLR2 and TLR4 on circulating monocytes has been shown to be increased in acute myocardial infarction and unstable angina patients compared to healthy control patients [9][10][11]. Given that TLR expression has been implicated atherosclerosis progression, it is likely that the magnitude of TLR induced release of inflammatory cytokines, i.e.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Is Toll-like receptor responsiveness a marker and predictor of coronary artery disease?

Björkbacka

2014

Atherosclerosis

View full text Add to dashboard Cite

Activated toll-like receptor 4 in monocytes is associated with heart failure after acute myocardial infarction

Cited by 117 publications

References 27 publications

Toll-Like Receptor-4 Modulates Survival by Induction of Left Ventricular Remodeling after Myocardial Infarction in Mice

Toll-Like Receptor-4 Modulates Survival by Induction of Left Ventricular Remodeling after Myocardial Infarction in Mice

Inflammatory Biomarkers for Persistent Fatigue in Breast Cancer Survivors

Is Toll-like receptor responsiveness a marker and predictor of coronary artery disease?

Contact Info

Product

Resources

About