The IL-33/ST2 pathway, inflammation and atherosclerosis: Trigger and target?

Aimo, Alberto; Migliorini, Paola; Vergaro, Giuseppe; Franzini, Maria; Passino, Claudio; Maisel, Alan; Emdin, Michele

doi:10.1016/j.ijcard.2018.05.056

Cited by 49 publications

(43 citation statements)

References 40 publications

(64 reference statements)

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“…The cardioprotective effect of IL-33 is abolished in ST2-null mice [15]. IL-33 also reduces the formation of foam cells and the development of atherosclerosis by blunting the Th1 and M1 immune responses, while sST2 has deleterious effects by sequestering IL-33 [16]. Moreover, IL-33 prevents cardiomyocyte apoptosis, decreases myocardial fibrosis and myocyte hypertrophy and impedes the atherosclerotic process [12,[17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Alteration of the IL-33-sST2 pathway in hypertensive patients and a mouse model

et al. 2019

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Inflammatory cells play an important role in the occurrence of hypertension. Recent studies have demonstrated that interleukin-33/suppression of tumorigenicity 2 (IL-33/ST2) signaling plays a critical role in the pathogenesis of several cardiovascular diseases. We aimed to evaluate the association of IL-33 and its receptor levels with the occurrence of hypertension in angiotensin II (Ang II)-infused mice using microarray analysis and validated our results in human specimens. Male wild-type mice were infused with Ang II (1500 ng/kg/min) for 1, 3 and 7 days. Patients with essential hypertension (EH) (n = 166) and healthy control subjects (n = 306) were enrolled. Levels of IL-33 and ST2 mRNAs in serum and peripheral blood mononuclear cells (PBMCs) were analyzed by Luminex assay or ELISA and qPCR analysis. We found that IL-33 expression was significantly increased in the aortas of mice receiving Ang II infusion compared with that of control mice. In contrast, the levels of IL-33 in serum and PBMCs were not significantly different between hypertensive patients and normal controls. However, the levels of soluble ST2 (sST2) in serum and PBMCs were markedly higher in hypertensive patients than in controls (P < 0.001 and P = 0.014, respectively). In addition, the ST2L level in PBMCs was also significantly decreased in hypertensive patients (P = 0.028). Further, logistic analysis showed that the odds ratios of having hypertension based on sST2 levels in serum and PBMCs were 9.714 and 2.244 (P = 0.013 and P = 0.024, respectively) compared with the control group. Above all, sST2 acted as a risk factor for the occurrence of hypertension and may be a promising novel predictive marker for EH.

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Section: Introductionmentioning

confidence: 99%

Alteration of the IL-33-sST2 pathway in hypertensive patients and a mouse model

et al. 2019

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“…ST2 acts as a decoy receptor for IL-33, thus blocking its protective effects. It has been reported that mice treated with soluble ST2 developed signi cantly larger atherosclerotic plaques in the aortic sinus of the ApoE(-/-) mice compared with the control mice [23].These results suggested that ST2 may be proposed as a marker of plaque burden and predictors of future cardiovascular event [24].Although the above data suggest that ST2 has a role in the prognosis of patients presenting with an acute coronary syndrome, whether ST2 contributes to cardiovascular risk prediction in a large scale CAD patients during a long-term follow up remains uncertain.…”

Section: Discussionmentioning

confidence: 92%

Prognostic value of ST2 for MACEs and all-cause mortality in patients with coronary artery disease during a long-term follow up

M¹,

H²,

Duan³

et al. 2020

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PurposeST2 has been proved the prognostic value in acute coronary syndrome (ACS), its prognostic value to predict cardiac events in established coronary artery disease (CAD) patients is unknown. The study ought to investigate the prognostic value of ST2 in patients with established coronary artery disease.MethodsA total of 3650 consecutive patients were included in the study. The primary end point was major adverse cardiovascular events (MACEs). The secondary end point was all-cause death. To explore competing risks, cause-specific hazard ratios were obtained using Cox regression models.ResultsDuring a median follow up of 6.4 years, there were 775 patients had the occurrence of MACEs and 275 patients died. Kaplan–Meier survival estimates indicated that the patients with higher level of ST2 (ST2 > 19 ng/ml) had a significantly increased risk of MACEs (log-rank p<0.001)and all-cause death(log-rank p<0.001). After adjustment for potential confounders, multiple COX regression models showed that higher level of ST2 was an independent predictor in developing MACEs(HR 1.31; 95% CI: 1.13–1.52; p<0.001) and all-cause death(HR 1.78; 95% CI: 1.38–2.30; p<0.001). We saw a significant increase of AUC in ROC curve after addition of GDF-15 to a clinical model 0.586 vs 0.619 For MACEs (p<0.001).For long-term all-cause death the increase of AUC 0.766 vs 0.642 (95% CI 0.787–0.846(p<0.001).ConclusionHigher level of ST2 is significantly associated with long-term all-cause death, MACEs and provides incremental prognostic value beyond traditional risks factors.

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“…Patients within 24 h after symptom onset were prospectively enrolled based on the TIA/ischemic stroke database of the First Affiliated Hospital of Zhengzhou University. The 1-year prognostic outcomes were composite adverse events (including ischemic and hemorrhagic stroke, myocardial infarction, and all-cause death) and a combination of major disability and death [modified Rankin Scale (mRS), [3][4][5][6]. Cox proportional hazard and logistic regression models were used to evaluate the association between serum sST2 and TIA/ischemic stroke prognosis.…”

Section: Methodsmentioning

confidence: 99%

Serum soluble ST2 is a predictor for poor long-term prognosis after transient ischemic attack and ischemic stroke: a cohort study

Tian

Guo

Wang

et al. 2019

Preprint

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Background Soluble ST2 (sST2) is a novel inflammation marker for the prediction of adverse outcomes in patients with cardiovascular disease and diabetes mellitus. The aim of the present study was to examine the predictive value of serum sST2 for prognostic outcomes in patients with transient ischemic attack (TIA)/ischemic stroke.Methods Patients within 24 h after symptom onset were prospectively enrolled based on the TIA/ischemic stroke database of the First Affiliated Hospital of Zhengzhou University. The 1-year prognostic outcomes were composite adverse events (including ischemic and hemorrhagic stroke, myocardial infarction, and all-cause death) and a combination of major disability and death [modified Rankin Scale (mRS), 3-6]. Cox proportional hazard and logistic regression models were used to evaluate the association between serum sST2 and TIA/ischemic stroke prognosis. The C statistic, net reclassiﬁcation index (NRI), and integrated discrimination index (IDI) were used to present improvement in risk classification.Results Serum sST2 levels were positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores. Kaplan-Meier analysis indicated a significantly different risk in composite adverse events between patients with higher and those with lower levels of sST2 (P=0.006). Serum sST2 was an independent predictor for composite adverse events (HR: 2.517, 95% CI: 1.279-4.956, P=0.008) and major disability or death (OR: 3.126, 95% CI: 1.452-6.728, P=0.004) after multivariate adjustment. The addition of the sST2 to the NIHSS score significantly improved the predictive value for prognostic outcomes in patients with TIA/ischemic stroke (C statistic: 0.021, IDI: 1.91%, P=0.042 for composite adverse events; NRI: 32.82%, P=0.042 for major disability or death).Conclusions Serum sST2 levels were positively associated with the severity of TIA/ischemic stroke and could independently predict composite adverse events and major disability or death, indicating that sST2 may be a potential prognostic marker for TIA/ischemic stroke.

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The IL-33/ST2 pathway, inflammation and atherosclerosis: Trigger and target?

Cited by 49 publications

References 40 publications

Alteration of the IL-33-sST2 pathway in hypertensive patients and a mouse model

Alteration of the IL-33-sST2 pathway in hypertensive patients and a mouse model

Prognostic value of ST2 for MACEs and all-cause mortality in patients with coronary artery disease during a long-term follow up

Serum soluble ST2 is a predictor for poor long-term prognosis after transient ischemic attack and ischemic stroke: a cohort study

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