Objective. More recently, evidence showed that the novel anti-inflammatory cytokine interleukin- (IL-) 37 was expressed in the foam-like cells of atherosclerotic coronary and carotid artery plaques, suggesting that IL-37 is involved in atherosclerosis-related diseases. However, the plasma levels of IL-37 in patients with acute coronary syndrome (ACS, including unstable angina pectoris and acute myocardial infarction) have yet to be investigated. Methods. Plasma IL-37, IL-18, and IL-18BP levels were measured in 50 patients with stable angina pectoris (SAP), 75 patients with unstable angina pectoris (UAP), 67 patients with acute myocardial infarction (AMI), and 65 control patients. Results. The plasma IL-37, IL-18, and IL-18BP levels were significantly increased in ACS patients compared to SAP and control patients. A correlation analysis showed that the plasma biomarker levels were positively correlated with each other and with the levels of C-reactive protein (CRP), N-terminal probrain natriuretic peptide (NT-proBNP), and left ventricular end-diastolic dimension (LVEDD) but negatively correlated with left ventricular ejection fraction (LVEF). Furthermore, the plasma IL-37, IL-18, and IL-18BP had no correlation with the severity of the coronary artery stenosis. Conclusions. The results indicate that the plasma IL-37 levels are associated with the onset of ACS.

Background Recent evidence has demonstrated that interleukin 12p35 knockout (IL-12p35 KO) is involved in cardiac diseases by regulating the inflammatory response. The involvement of inflammatory cells has also been observed in doxorubicin (DOX)-induced cardiac injury. This study aimed to investigate whether IL-12p35 KO affects DOX-induced cardiac injury and the underlying mechanisms. Methods First, the effect of DOX treatment on cardiac IL-12p35 expression was assessed. In addition, to investigate the effect of IL-12p35 KO on DOX-induced cardiac injury, IL-12p35 KO mice were treated with DOX. Because IL-12p35 is the mutual subunit of IL-12 and IL-35, to determine the cytokine that mediates the effect of IL-12p35 KO on DOX-induced cardiac injury, mice were given phosphate-buffered saline (PBS), mouse recombinant IL-12 (rIL-12) or rIL-35 before treatment with DOX. Results DOX treatment significantly increased the level of cardiac IL-12p35 expression. In addition, IL-12p35 KO mice exhibited higher serum and heart lactate dehydrogenase levels, higher serum and heart creatine kinase myocardial bound levels, and greater cardiac dysfunction than DOX-treated mice. Furthermore, IL-12p35 KO further increased M1 macrophage and decreased M2 macrophage differentiation, aggravated the imbalance of oxidants and antioxidants, and further activated the mitochondrial apoptotic pathway and endoplasmic reticulum stress autophagy pathway. Both rIL-12 and rIL-35 protected against DOX-induced cardiac injury by alleviating the inflammatory response, oxidative stress, apoptosis and autophagy. Conclusions IL-12p35 KO aggravated DOX-induced cardiac injury by amplifying the levels of inflammation, oxidative stress, apoptosis and autophagy. (234 words).

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Background Previous studies demonstrated that the subsets of CD4+ T helper (Th) cells are closely related to vascular diseases, including atherosclerosis and hypertension. This study is aimed at investigating the circulating Th1, Th2, Th9, Th17, Th22, and Treg levels in aortic dissection (AD) patients. Methods Blood samples from AD (n = 56) and non-AD (NAD, n = 24) patients were collected, and the circulating levels of Th1, Th2, Th9, Th17, Th22, and Treg cells and their transcription factors and functional cytokines were measured by flow cytometric analysis, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assays, respectively. In addition, the human aortic vascular smooth muscle cells (HASMCs) were treated with saline, angiotensin II (Ang II), or plasma from AD patients. Results Compared with the levels in the NAD group, the Th1, Th9, Th17, Th22, and their transcription factor levels were increased and the Th2, Treg, and their transcription factor levels exhibited a decreasing trend in AD patients. In addition, higher IFN-γ, IL-9, IL-17, and IL-22 levels and lower IL-4 and IL-35 levels were observed in AD patients. Simple linear regression analysis and binary logistic regression analysis suggested that Th1/IFN-γ, IL-9, Th17/IL-17, and Th22/IL-22 positively regulated the occurrence of AD, while Th2/IL-4 and Treg/IL-35 negatively regulated the occurrence of AD. Plasma from AD patients further increased Bax mRNA levels but decreased Bcl2 and α-SMA mRNA levels in Ang II-treated HASMCs. Conclusions Changes in Th1, Th2, Th9, Th17, Th22, and Treg activity are associated with the onset of AD. Different subsets of CD4+ T cells play different roles in the presence of AD.

BackgroundAccumulating evidence shows that the novel anti-inflammatory cytokine IL-35 can efficiently suppress effector T cell activity and alter the progression of inflammatory and autoimmune diseases. The two subunits of IL-35, EBI3 and p35, are strongly expressed in human advanced plaque, suggesting a potential role of IL-35 in atherosclerosis and coronary artery disease (CAD). However, the plasma levels of IL-35 in patients with CAD have yet to be investigated.MethodsPlasma IL-35, IL-10, TGF-β1, IL-12 and IL-27 levels were measured using an ELISA in 43 stable angina pectoris (SAP) patients, 62 unstable angina pectoris (UAP) patients, 56 acute myocardial infarction (AMI) patients and 47 chest pain syndrome patients as a control group.ResultsThe results showed that plasma IL-35 levels were significantly decreased in the SAP group (90.74±34.22 pg/ml), the UAP group (72.20±26.63 pg/ml), and the AMI group (50.21±24.69 pg/ml) compared with chest pain syndrome group (115.06±32.27 pg/ml). Similar results were also demonstrated with IL-10 and TGF-β1. Plasma IL-12 and IL-27 levels were significantly increased in the UAP group (349.72±85.22 pg/ml, 101.75±51.42 pg/ml, respectively) and the AMI group (318.05±86.82 pg/ml, 148.88±68.45 pg/ml, respectively) compared with chest pain syndrome group (138.68±34.37 pg/ml, 63.60±22.75 pg/ml, respectively) and the SAP group (153.84±53.86 pg/ml, 70.84±38.77 pg/ml, respectively). Furthermore, lower IL-35 levels were moderately positively correlated with left ventricular ejection fraction (LVEF) in CAD patients (R = 0.416, P<0.01), whereas higher IL-27 levels were weakly negatively correlated with LVEF in CAD patients(R = −0.205, P<0.01).ConclusionsThe results of the present study show that circulating IL-35 is a potentially novel biomarker for coronary artery disease. Regulating the expression of IL-35 also provides a new possible target for the treatment of atherosclerosis and CAD.