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BackgroundAcute myocardial infarction (AMI) is a major contributor of heart failure (HF). Peripheral blood mononuclear cells (PBMCs), mainly monocytes, are the essential initiators of AMI-induced HF. The powerful biomarkers for early identification of AMI patients at risk of HF remain elusive. We aimed to identify monocyte-related critical genes as predictive biomarkers for post-AMI HF.MethodsWe performed weighted gene co-expression network analysis (WGCNA) on transcriptomics of PBMCs from AMI patients who developed HF or did not. Functional enrichment analysis of genes in significant modules was performed via Metascape. Then we obtained the single-cell RNA-sequencing data of recruited monocytes/macrophages from AMI and control mice using the Scanpy and screened 381 differentially expressed genes (DEGs) between the two groups. We validated the expression changes of the 25 genes in cardiac macrophages from AMI mice based on bulk RNA-sequencing data and PBMCs data mentioned above.ResultsIn our study, the results of WGCNA showed that two modules containing 827 hub genes were most significantly associated with post-AMI HF, which mainly participated in cell migration, inflammation, immunity, and apoptosis. There were 25 common genes between DEGs and hub genes, showing close relationship with inflammation and collagen metabolism. CUX1, CTSD and ADD3 exhibited consistent changes in three independent studies. Receiver operating characteristic curve analysis showed that each of the three genes had excellent performance in recognizing post-AMI HF patients.ConclusionOur findings provided a set of three monocyte-related biomarkers for the early prediction of HF development after AMI as well as potential therapeutic targets of post-AMI HF.

Angiogenesis is an essential pathological feature of vulnerable atherosclerotic plaque. Exosome‑derived microRNAs (miRNAs or miRs) have been proven to be important regulators of angiogenesis. However, the role of exosomes, which are secreted by endothelial cells (ECs) under conditions of oxidative stress, in angiogenesis remain unclear. The present study aimed to investigate the effects and mechanism of oxidative stress‑activated endothelial‑derived exosomes in angiogenesis. Exosomes were isolated from H2O2‑stimulated human umbilical vein ECs (HUVECs; termed Exo-H2O2) by differential centrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis and western blot analysis. Exo-H2O2 enhanced HUVEC proliferation, migration and tube formation, as determined by EdU incorporation assay, scratch wound migration assay and tube formation assay, respectively. miR‑92a‑3p was identified as the predominantly downregulated miRNA in the Exo-H2O2‑treated HUVECs by small RNA sequencing, and the expression of primary miR‑92a (pri‑miR‑92a‑1) was also decreased, as shown by RT‑qPCR. Similarly, the inhibition of miR‑92a‑3p promoted angiogenesis in vitro and in vivo. miR‑92a‑3p overexpression blocked the pro‑angiogenic effects of Exo-H2O2 on target ECs. Tissue factor (TF), a molecule involved in angiogenesis, was increased in HUVECs in which miR‑92a‑3p expression was downregulated, as shown by mRNA sequencing. TF was also predicted as a target of miR‑92a‑3p by using the RNAhybrid program. The overexpression or suppression of miR‑92a‑3p modified TF expression at both the mRNA and protein level, as measured by RT‑qPCR and western blot analysis, respectively. Luciferase reporter assays suggested that miR‑92a‑3p inhibited TF expression by binding to the 3' untranslated region of TF. On the whole, the findings of the present study demonstrate that exosomes released from oxidative stress‑activated ECs stimulate angiogenesis by inhibiting miR‑92a‑3p expression in recipient ECs, and TF may be involved in the regulatory effects of miR‑92a‑3p on angiogenesis.

Objective: To compare the plaque composition between stable and unstable plaques, characterize unstable plaque by using iMap-intravascular ultrasound (IVUS), and quantify the diagnostic criteria for unstable plaque. Methods: Thirty-three acute coronary syndrome (ACS) patients who had undergone coronary angiography and IVUS from February 19, 2014 to December 19, 2014 at Peking University People’s Hospital were enrolled in the study. Baseline data were collected. The patients were divided into two groups according to their gray-scale IVUS imaging, stable plaque and unstable plaque. A difference-in-difference evaluation was performed using the baseline data and off-line iMap imaging results between the two groups. A receiver operating characteristic (ROC) curve was constructed to obtain the optimal cut-off value to diagnose unstable plaque. Results: Percentages of fibrotic and necrotic tissues, absolute values of lipidic, necrotic, and calcified tissues, and plaque burden were independent predictors for unstable plaque. Absolute necrotic area was the best predictor and exhibited the highest diagnostic value for plaque vulnerability (area under the curve (AUC)=0.806, P=0.000, 95% CI (0.718, 0.894)). The cut-off score for predicting unstable plaque was 4.0 mm2. Conclusions: This study attempted to propose a cut-off value based on absolute necrotic area using iMap-IVUS to predict plaque vulnerability in patients with ACS. This score might provide a valuable reference for diagnosing unstable plaque.

Atherosclerotic plaque growth requires angiogenesis, and acute coronary syndrome (ACS) is usually triggered by the rupture of unstable atherosclerotic plaques. Previous studies have identified typically circulating microRNA (miRNA/miR) profiles in patients with ACS. miRNAs serve important roles in the pathophysiology of atherosclerotic plaque progression. The present study aimed to investigate the potential role and mechanism of miR‑19b in plaque stability. miRNA array data indicated that 28 miRNAs were differentially expressed in the plasma of patients with unstable angina (UA; n=12) compared with in control individuals (n=12), and miR‑19b exhibited the most marked upregulation. Circulating miR‑19b levels were further validated in another independent cohort, which consisted of 34 patients with UA and 24 controls, by quantitative polymerase chain reaction. Gene Ontology annotations of the predicted target genes of miR‑19b suggested that miR‑19b may be involved in endothelial cell (EC) proliferation, migration and angiogenesis, which was confirmed by Cell Counting kit‑8, wound healing and tube formation assays in the present study. Finally, the present study indicated that miR‑19b may suppress signal transducer and activator of transcription 3 (STAT3) tyrosine phosphorylation and transcriptional activity in ECs, as determined by western blot analysis and luciferase reporter assay. In conclusion, the present study revealed that increased miR‑19b expression may delay unstable plaque progression in patients with UA by inhibiting EC proliferation, migration and angiogenesis via the suppression of STAT3 transcriptional activity.

A 73-year-old woman was admitted with progressive chest pain for 2 years. She had a history of hypertension for 9 years. Findings on physical examination were normal. Low-density lipoprotein cholesterol level was 3.04 mmol/l. Results on electrocardiography and echocardiography were normal. Cardiac