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• IL-20 and its receptors were increased in arterial wall dissection from AAD patients. • The plasma IL-20 were significantly higher in the AAD patients. • IL-20 may contribute to the inflammatory pathogenesis of AAD. Acute aortic dissection (AAD) is the most devasting cardiovascular disease associated with high mortality. The occurrence and progression of AAD can be regulated by inflammatory processes, and further understanding of this inflammatory pathogenesis may improve the treatment of AAD. Interleukin 20 (IL-20), as an inflammatory mediator, has been demonstrated to be associated with several inflammatory diseases. However, the association between IL and 20 and AAD is still unknown. Five aortic dissection tissue samples and five control aortic tissue samples were evaluated in our study. The expression of IL-20 and its receptor subunits (IL-20Rα and IL-20Rβ) was detected by immunofluorescence staining. From January 2018 to March 2018, 70 consecutive AAD patients and 25 non-AAD (NAD) patients were enrolled in this study. Diagnosis was based on computed tomography angiography (CTA) results. Blood samples were obtained from the patients on the first day of hospitalization. Plasma IL-20, TNF-α and IL-6 concentrations were evaluated with enzyme-linked immunosorbent assay (ELISA) kits. The expression levels of IL-20 and its receptor subunits (IL-20Rα and IL-20Rβ) were increased in the sites of arterial wall dissection in the AAD patients. In a separate group, the plasma IL-20, TNF-α and IL-6 concentrations were significantly higher in the AAD patients than in the non-AAD patients. Spearman's correlation analysis showed that plasma IL-20 was positively correlated with plasma TNF-α and IL-6, D-dimer, C-reaction protein (CRP), creatinine, fasting blood glucose, systolic blood pressure (SBP), and diastolic blood pressure (DBP). Multiple linear regression revealed that IL-20, in addition to IL-6, glucose, CRP and D-dimer, was independently associated with the presence of AAD. IL-20 was closely associated with the presence of AAD. IL-20 may contribute to the inflammatory pathogenesis of AAD. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that bone morphogenetic proteins (BMPs) play important roles in cardiovascular diseases, including atherosclerosis, artery calcification, myocardial remodeling, pulmonary arterial hypertension, and diabetic cardiomyopathy. Kielin/chordin-like protein (KCP) is a secreted protein that regulates the expression and function of BMPs. However, the role of KCP in cardiac aging remains unknown. In this study, we aimed to investigate the role of KCP in cardiac aging and its possible mechanisms. Echocardiogram showed that heart function was impaired in aged mice (24 months). In addition, analysis of heart structure showed that KCP knockout (KO) aggravated cardiac remodeling in aged mice. Moreover, KCP KO increased p-smad2/3 and TGF-β expression, while decreased BMP-2 expression in aged mice. Furthermore, KCP KO increased the expression of cardiac senescence-related proteins in aged mice. KCP KO aggravated the imbalance of oxidants and antioxidants and increased the expression of proinflammatory cytokines and cardiomyocyte apoptosis in aged mice. Our study demonstrated that KCP KO aggravated cardiac aging in mice by increasing the levels of oxidative stress, inflammation, and cardiomyocyte apoptosis. Key message: KCP KO aggravated aging-related cardiac dysfunction and remodeling in male mice. KCP KO aggravated cardiac aging by increasing the levels of oxidative stress, inflammation, and cardiomyocyte apoptosis. [ABSTRACT FROM AUTHOR]

Efferocytosis is defined as the clearance of apoptotic cells (ACs) in physiological and pathological states and is performed by efferocytes, such as macrophages. Efferocytosis can lead to the resolution of inflammation and restore tissue homoeostasis; however, the mechanisms of efferocytosis in determining inflammation resolution are still not completely understood, and the effects of efferocytosis on other proresolving properties need to be explored and explained. In this review, the process of efferocytosis will be summarized briefly, and then these mechanisms and effects will be thoroughly discussed. In addition, the association between mechanisms of efferocytosis in determining resolution of inflammation and cardiovascular diseases will also be reviewed, as an understanding of this association may provide information on novel treatment targets. [ABSTRACT FROM AUTHOR]

Increased inflammation is the key mechanism that mediates sepsis induced cardiac injury. Resolvin D1 (RvD1), a bioactive lipid mediator synthesized from docosahexaenoic acid, can attenuate the severity of many inflammation‐related diseases through anti‐inflammatory and pro‐resolving properties. However, the protective role of RvD1 in sepsis induced cardiac injury remains unclear. Mice were randomly divided into three groups: the control group, LPS group and RvD1 + LPS group. LPS (10 mg/kg, i.p.) was used to establish a sepsis‐induced cardiac injury model. RvD1 (5 ug/kg, i.p.) was injected 30 min before LPS injection. RvD1 treatment significantly attenuated the deteriorated cardiac function and cardiac injury induced by LPS, as evidenced by the improved left ventricular ejection fraction, serum levels of cardiac injury markers and severity of cardiomyocyte apoptosis. In addition, RvD1 treatment significantly attenuated the infiltration of pro‐inflammatory M1 macrophages and expression of inflammatory cytokines in the heart. Mechanistically, the attenuated activation of NK‐κB and MAPK signaling mediated the anti‐inflammatory and antiapoptotic effects of RvD1. In addition, LPS‐induced infiltration of neutrophils and M1 macrophages in the spleen was significantly attenuated by the RvD1 treatment. Results of the present study suggest that RvD1 protects the heart against LPS‐induced injuries by attenuating the local and systemic inflammatory response, highlighting the therapeutic effects of RvD1 in sepsis‐induced cardiac injury. [ABSTRACT FROM AUTHOR]

Abstract Background Interleukin (IL)-22 plays important roles in the development of arterial disease, including atherosclerosis and hypertension. However, the relationship between IL-22 and acute thoracic aortic dissection (TAD) remains unknown. Methods Blood samples were collected from patients with chest pain who underwent computed tomography angiography of the thoracic aorta but had no known preoperative diagnosis of coronary artery disease, peripheral artery disease, arthritis, and/or membranous nephropathy. Patients were divided into non-AD (NAD) and TAD groups, and the plasma concentrations of IL-22, IL-6 and tumor necrosis factor (TNF)-α were measured. In addition, aortic tissue samples from acute TAD patients and normal donors were collected, and the expression levels of IL-22 and IL-22 receptor 1 (IL-22R1) were measured. Results IL-22, IL-6 and TNF-α levels were significantly higher in acute TAD patients than in NAD patients (IL-22, NAD group: 27.0 (19.1, 38.6) pg/ml vs. TAD group: 32.9 (20.6, 58.3) pg/ml, p < 0.0001). The correlation analysis showed that IL-22 levels were positively correlated with levels of IL-6, TNF-α, fasting glucose, blood pressure, white blood cells, C-reactive proteins and D-dimers. Binary logistic regression analyses showed that IL-22 was independently associated with the presence of acute TAD (OR 1.169, 95% CI 1.069 to 1.277; p = 0.001). In addition, compared with aortic tissue of normal controls, TAD aortas showed increased expression of IL-22 and IL-22R1, especially in the torn section (IL-22, non-torn section: 2.8 ± 0.5/HPF vs. torn section 2.8 ± 0.5/HPF, p < 0.001). Additionally, macrophage but not T lymphocyte infiltration was significantly increased in the torn section (Macrophage, non-torn section: 2.2 ± 0.6/HPF vs. torn section 5.7 ± 1.2/HPF, p < 0.001; T lymphocyte, non-torn section: 2.7 ± 0.9/HPF vs. torn section 2.4 ± 0.5/HPF, p = 0.28), as evidenced by increased positive staining for the macrophage marker CD68, as opposed to the T cell marker CD3. Conclusion IL-22 levels may correlate with the presence of acute TAD. Highlights • IL-22 expression was significantly increased both in the plasma and aortas of TAD. • IL-22 was independently associated with the presence of acute TAD and regulation of inflammation was the possible mechanism. • IL-22 may be a new biomarker for TAD and be useful for the diagnosis of TAD. [ABSTRACT FROM AUTHOR]

Background Interleukin (IL) 11 is closely related to tumor and hematological system diseases. Recent studies have demonstrated that IL-11 also participates in cardiovascular diseases, including ischemia-reperfusion mediated heart injury and acute myocardial infarction. This study aimed to investigate whether IL-11 is involved in acute thoracic aortic dissection (TAD). Methods Aortic tissue samples from normal donors and acute TAD patients were collected, and the expression of IL-11 in all aortic tissue was analyzed. In addition, blood samples from patients with chest pain were collected and divided into a non-AD (NAD) group and a TAD group according to the results of computed tomography angiography of the thoracic aorta. The plasma IL-11, IL-17 and interferon (IFN) γ in all blood samples were measured. Results Compared with aortic tissue of normal controls, IL-11 was significantly increased in aortic tissue of acute TAD patients, especially in the torn section. The IL-11 was derived from aorta macrophages in TAD. In addition, the plasma IL-11, IL-17 and IFN-γ were significantly higher in acute TAD patients than in NAD patients, and the correlation analysis showed that IL-11 levels were positively correlated with levels of IFN-γ, IL-17, glucose, systolic blood pressure, diastolic blood pressure, white blood cells, C-reactive proteins and D-dimers. Binary logistic regression analyses showed that elevated IL11 in patients who may have diagnostic value of TAD, but less that D-dimer. Conclusion IL-11 was increased in thoracic aorta and plasma of TAD patients and may be a promising biomarker for diagnosis in patients with TAD. [ABSTRACT FROM AUTHOR]

[Display omitted] Several interleukins (ILs) have been demonstrated to participate in cardiac injury. This study aimed to investigate whether IL-27p28 plays a regulatory role in doxorubicin (DOX)-induced cardiac injury by regulating inflammation and oxidative stress. Dox was used to establish a mouse cardiac injury model, and IL-27p28 was knocked out to observe its role in cardiac injury. In addition, monocytes were adoptively transferred to clarify whether monocyte-macrophages mediate the regulatory role of IL-27p28 in DOX-induced cardiac injury. IL-27p28 knockout significantly aggravated DOX-induced cardiac injury and cardiac dysfunction. IL-27p28 knockout also upregulated the phosphorylation levels of p65 and STAT1 and promoted M1 macrophage polarization in DOX-treated mice, which increased cardiac inflammation and oxidative stress. Moreover, IL-27p28-knockout mice that were adoptively transferred WT monocytes exhibited worse cardiac injury and cardiac dysfunction and higher cardiac inflammation and oxidative stress. IL-27p28 knockdown aggravates DOX-induced cardiac injury by worsening the M1 macrophage/M2 macrophage imbalance and its associated inflammatory response and oxidative stress. [ABSTRACT FROM AUTHOR]

[Display omitted] • 1.MCC950 treatment reverses cardiac dysfunction in mice after TAC surgery. • 2.MCC950 attenuates cardiac hypertrophy and fibrosis induced by pressure overload. • 3.MCC950 attenuates pressure overload-induced myocardial inflammation. • 4.MCC950 reduces the infiltration of both M1 and M2 macrophages after TAC surgery. Activation of the NLRP3 inflammasome promotes pathological cardiac remodeling induced by pressure overload. However, the therapeutic effects of NLRP3 inhibition after cardiac remodeling remain unknown. The present study aimed to investigate whether the selective NLRP3 inhibitor, MCC950, could reverse transverse aortic constriction (TAC)-induced cardiac remodeling. Mice were divided into four groups based on the treatment given: sham, sham + MCC950, TAC, and TAC + MCC950. MCC950 (10 mg/kg, intraperitoneal injection, once per day) was administered from two weeks after TAC or sham surgery for four weeks. Echocardiography, histological analysis, RT-PCR, and Western blotting were performed to explore the function of MCC950 after TAC. We found that MCC950 reversed cardiac dysfunction after TAC. MCC950 attenuated cardiac hypertrophy by down-regulating calcineurin expression and inhibiting MAPK activation. Further, it also alleviated cardiac fibrosis post-TAC by inhibiting the TGF-β/Smad4 pathway, and reduced cardiac inflammation and macrophage infiltration post-TAC, including both M1 and M2 macrophages. Taken together, MCC950 can attenuate cardiac remodeling due to pressure overload by inhibiting hypertrophy, fibrosis, and inflammation. Our study provides a basis for the clinical application of NLRP3 inhibitors in the treatment of non-ischemic heart failure. [ABSTRACT FROM AUTHOR]

Interleukin (IL) 9 is a pleiotropic cytokine, and recent studies have demonstrated that IL-9 is associated with several cardiovascular diseases, via regulation of the inflammatory response. Doxorubicin (DOX) is known to induce severe cardiac injury and dysfunction by enhancing inflammation. This study aimed to investigate the role of IL-9 in DOX-induced cardiotoxicity. DOX was used to induce cardiac dysfunction and the expression of IL-9 in the murine cardiac tissues was measured. The mice were intraperitoneally injected with recombinant mouse IL-9 (rmIL-9) or anti-IL-9 neutralizing antibody (IL-9nAb) for investigating the effect of IL-9 on DOX-induced cardiac injury and dysfunction. The messenger ribonucleic acid (mRNA) expression levels of the pro-inflammatory cytokines were determined in each group by quantitative real-time polymerase chain reaction (RT-qPCR). The effect of rmIL-9 or IL-9nAb on DOX-induced apoptosis was determined both in vivo and vitro. IL-9 levels significantly increased in the heart following DOX injection. Cardiac injury and dysfunction were induced by DOX, and treatment with IL-9nAb significantly alleviated DOX-induced injury, whereas rmIL-9 administration aggravated the cardiac damage. IL-9nAb decreased the expression of pro-inflammatory cytokines in the DOX-treated mice, while rmIL-9 administration increased the levels of pro-inflammatory cytokines. IL-9nAb reduced DOX-induced myocardial apoptosis, whereas rmIL-9 administration produced the opposite results. Additionally, IL-9nAb mitigated the DOX-induced apoptosis in H9C2 cells, while administration of rmIL-9 produced the opposite effect. Our results demonstrated that IL-9 aggravated DOX-induced cardiac injury and dysfunction by promoting the inflammatory response and cardiomyocyte apoptosis. [ABSTRACT FROM AUTHOR]