Therapies aimed at minimizing adverse remodeling in cardiovascular diseases on a molecular and cellular basis are urgently needed. Exosomes are nanosized lipid vesicles released from various cells that are able to mediate intercellular signaling and communication via their cargos. It has been increasingly demonstrated that exosomes from cardiomyocytes or stem/progenitor cells can promote cardiac repair and regeneration, but their mechanism has not been fully explained. Immune responses mediated by immune cells also play important and complicated roles in the progression of various cardiovascular diseases such as myocardial infarction and atherosclerosis. Exosomes derived from immune cells have shown pleiotropic effects on these pathological states, whether similar to or different from their parent cells. However, the underlying mechanism remains obscure. In this review, we first describe the biological characteristics and biogenesis of exosomes. Then we critically examine the emerging roles of exosomes in cardiovascular disease; the exosomes we focus on are derived from immune cells such as dendritic cells, macrophages, B cells, T cells, as well as neutrophils and mast cells. Among the cardiovascular diseases we discuss, we mainly focus on myocardial infarction and atherosclerosis. As active intercellular communicators, exosomes from immune cells may offer prospective diagnostic and therapeutic value in cardiovascular disease.

Activation of endothelial cells is the first step of atherosclerosis. The current authors have previously reported that exosomes from mature dendritic cells (mDC-exo) participate in endothelial inflammation and atherosclerosis through membrane tumor necrosis factor-α mediated the nuclear factor (NF)-κB signaling pathway. However, whether mDC-exo shuttled microRNAs (miRNAs/miRs) play a role in endothelial inflammation remains unknown. In this study, mDC-exo were co-cultured with human umbilical vein endothelial cells (HUVECs) and the expression of adhesion molecules, such as vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and E-Selectin was investigated. Then the expression of miRNAs in DC-exo was explored and the role of miR-146a in endothelial inflammation was investigated. mDC-exos were first demonstrated to increase endothelial expression of adhesion molecules through a quick activation of the NF-κB signaling pathway. Then it was demonstrated that HUVECs resistant to a second stimulation after the first stimulation by mDC-exo. A set of miRNAs were targeted and their expression in HUVECs stimulated with mDC-exo was measured. Finally, it was confirmed that mDC-exo shuttles miR-146a into HUVECs and the shuttled miR-146a contributes to protect HUVECs from a second stimulation through inhibiting interleukin-1 receptor-associated kinase. These data suggest a negative feedback loop of inflammation regulation by DC-exo.

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ObjectiveCeramides are associated with coronary plaque vulnerability. We aim to investigate the potential diagnostic value of ceramides for acute coronary syndrome (ACS) in Chinese patients with chest pain.DesignProspective observational survey.SettingShanghai, China, 2016–2017.ParticipantsA total of 2773 patients with chest pain from four hospitals in Shanghai, China, between August 2016 and October 2017.Main outcome measuresPerformance of metabolites model in detection of ACS cases including ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable angina.ResultsPlasma levels of 12 ceramide molecules and corresponding ratios were compared between patients diagnosed with ACS and those without. Cer(d18:1/24:1(15Z))/Cer(d18:1/24:0) ratio, Cer(d18:1/14:0) and Cer(d18:1/22:0) were independent predictors of ACS after adjustment of traditional risk factors and high-sensitivecardiac troponin T. Receiver operating characteristic curve analysis showed a significant improvement in detecting ACS in the multivariable model with ceramides compared with that without (0.865 (0.840 to 0.889) vs 0.808 (0.776 to 0.841), p<0.001).ConclusionDistinct plasma ceramides are independent diagnostic predictors of ACS among patients with chest pain. Ceramides together with high-sensitive troponin and traditional factors showed great potential in identifying ACS among patients with chest pain.

Background NLR family CARD domain containing 5 (NLRC5) is involved the initiation and progression of several cancers. However, its role in hepatocellular carcinoma (HCC) is still unclear. This study aimed to explore the expression, clinical significance, and regulated gene sets of NLRC5 in HCC. Methods Data related to NLRC5 was extracted from The Cancer Genome Atlas (TCGA) database and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to verify the NLRC5 mRNA expression in HCC. Immunohistochemistry (IHC) and western blot were performed to detect the NLRC5 protein level in HCC. The clinical significance of NLRC5 was investigated after separating patients into NLRC5-positive and NLRC5-negative groups based on the IHC results. Gene set enrichment analysis (GSEA) was performed to detect gene sets regulated by NLRC5 in HCC. Results Increased NLRC5 mRNA and protein expression were found in HCC tissues compared to paracancerous tissues. Moreover, enhanced NLRC5 protein expression was associated with a higher presence rate of cirrhosis, a higher TNM stage, and a shorter 3-year overall survival (OS) of HCC participants. Finally, gene sets related to cancer metastasis were up-regulated in the NLRC5 high phenotype. Conclusions NLRC5 is a potential marker for the diagnosis and prognostic assessment of HCC.

Background: Whether the role of plasma heat shock protein 70 (HSP70) in acute myocardial infarction (AMI) is protective or detrimental remains debated, and the relationship between HSP70 and total occlusion remains elusive.Methods: A total of 112 patients with primary diagnosis of AMI and 52 patients with chronic coronary syndrome (CCS) were enrolled into the study. Plasma HSP70 level was determined by ELISA on day 1 and day 7 after the onset of AMI and was examined before angiography in patients with CCS. Peak NT-proBNP, high-sensitivity C-reactive protein (CRP), troponin T (cTnT), and left ventricular ejection fraction were measured.Results: Plasma HSP70 was significantly higher in CCS than AMI (P &lt; 0.0001), and it showed a significant decrease from day 1 to day 7 after AMI (P &lt; 0.01). Elevated HSP70 was associated with decreased levels of LDL-C (P &lt; 0.05), peak cTnT (R = −0.3578, P &lt; 0.0001), peak NT-proBNP (R = −0.3583, P &lt; 0.0001), and peak CRP (R = −0.3539, P &lt; 0.0001) and a lower diagnosis of AMI (R = −0.4016, P &lt; 0.0001) and STEMI (R = −0.3675, P &lt; 0.0001), but a higher diagnosis of total occlusion in target vessels (R = 0.1702, P &lt; 0.05). HSP70 may provide certain predictive value for the diagnosis of AMI, STEMI, and total occlusion in target vessels, and the area under the receiver operating characteristic curves were 0.7660, 0.7152, and 0.5984, respectively. HSP70 was also negatively associated with in-hospital stay (P &lt; 0.001) and positively correlated with left ventricular ejection fraction (LVEF) at 1-year follow-up (P &lt; 0.05), despite no association with in-hospital major adverse cardiovascular events (MACE).Conclusion: Plasma HSP70 level was found to decrease from day 1 to day 7 post-AMI, but the overall level of patients with AMI was lower than that of patients with CCS. However, the ability of HSP70 to identify clinically significant AMI and STEMI was moderate, and the predictive value to total occlusion was slight.

To investigate the prevention of cardiac remodelling and inflammatory immune response after myocardial infarction (MI) via ACEI regulating dendritic cells (DCs), we explored whether the protective effect of ACEI was repressed under hyperlipidemic environment. In vivo, the survival rate and left ventricular function of the mice were recorded on day 7 after MI. Tissue samples of the myocardium, spleen, bone marrow and peripheral blood were assessed for Ang II concentration, inflammatory cytokines and DCs expression. In vitro, DCs were treated with ox-LDL + Ang II, simulating the internal environment of MI in ApoE −/− mice to explore the mechanism involved in the DCs maturation and inflammation. Under hyperlipidemic circumstances, we found that the cardioprotective effect of ACEI was attenuated through regulating DCs maturation and inflammation after MI, affecting survival rate and left ventricular function. Effects of lisinopril on the release of spleen-derived DCs and myocardial infiltration were also reduced under hyperlipidemic conditions. In vitro, immune maturation and inflammation of DCs were further induced by ox-LDL on the basis of Ang II treatment, as indicated by the upregulation of CD83, CD86, and the expressions of cytokines and chemokines. Furthermore, ox-LDL could activate TLR4-MyD88 signalling pathway, promoting IRAK-4 and NF-κB. The present study demonstrated that ACEI reduced the recruitment of DCs to the infarct site, leading to a higher survival rate and improved function. However, this effect was inhibited under hyperlipidemic environment. TLR4-MyD88 signalling pathway may be responsible for the molecular mechanism involved in the immune maturation and inflammation of DCs induced by ox-LDL. K E Y W O R D Sangiotensin-converting enzyme inhibitor, dendritic cell, hyperlipidemia, myocardial infarction | 4083 MA et Al.

Background: Coronary artery disease (CAD) is the leading cause of cardiovascular death. The competitive endogenous RNAs (ceRNAs) hypothesis is a new theory that explains the relationship between lncRNAs and miRNAs. The mechanism of ceRNAs in the pathological process of CAD has not been fully elucidated. The objective of this study was to explore the ceRNA mechanism in CAD using the integrative bioinformatics analysis and provide new research ideas for the occurrence and development of CAD.Methods: The GSE113079 dataset was downloaded, and differentially expressed lncRNAs (DElncRNAs) and genes (DEGs) were identified using the limma package in the R language. Weighted gene correlation network analysis (WGCNA) was performed on DElncRNAs and DEGs to explore lncRNAs and genes associated with CAD. Functional enrichment analysis was performed on hub genes in the significant module identified via WGCNA. Four online databases, including TargetScan, miRDB, miRTarBase, and Starbase, combined with an online tool, miRWalk, were used to construct ceRNA regulatory networks.Results: DEGs were clustered into ten co-expression modules with different colors using WGCNA. The brown module was identified as the key module with the highest correlation coefficient. 188 hub genes were identified in the brown module for functional enrichment analysis. DElncRNAs were clustered into sixteen modules, including seven modules related to CAD with the correlation coefficient more than 0.5. Three ceRNA networks were identified, including OIP5-AS1-miR-204-5p/miR-211-5p-SMOC1, OIP5-AS1-miR-92b-3p-DKK3, and OIP5-AS1-miR-25-3p-TMEM184B.Conclusion: Three ceRNA regulatory networks identified in this study may play crucial roles in the occurrence and development of CAD, which provide novel insights into the ceRNA mechanism in CAD.