CD40-targeting magnetic nanoparticles for MRI/optical dual-modality molecular imaging of vulnerable atherosclerotic plaques.

BACKGROUND AND AIMS: Acute coronary syndrome caused by vulnerable plaque rupture or erosion is a leading cause of death worldwide. CD40 has been reported to be highly expressed in atherosclerotic plaques and closely related to plaque stability. Therefore, CD40 is expected to be a potential target for the molecular imaging of vulnerable plaques in atherosclerosis. We aimed to design a CD40-targeted magnetic resonance imaging (MRI)/optical multimodal molecular imaging probe and explore its ability to detect and target vulnerable atherosclerotic plaques. METHODS: CD40-Cy5.5 superparamagnetic iron oxide nanoparticles (CD40-Cy5.5-SPIONs), which comprise a CD40-targeting multimodal imaging contrast agent, were constructed by conjugating CD40 antibody and Cy5.5-N-hydroxysuccinimide ester with SPIONs. During this in vitro study, we observed the binding ability of CD40-Cy5.5-SPIONs with RAW 264.7 cells and mouse aortic vascular smooth muscle cells (MOVAS) after different treatments, using confocal fluorescence microscopy and Prussian blue staining. An in vivo study involving ApoE-/- mice fed a high-fat diet for 24-28 weeks was performed. 24 h after intravenous injection of CD40-Cy5.5-SPIONs, fluorescence imaging and MRI were performed. RESULTS: CD40-Cy5.5-SPIONs bind specifically to tumor necrosis factor (TNF)-α-treated macrophages and smooth muscle cells. Fluorescence imaging results showed that, compared with the control group and the atherosclerosis group injected with non-specific bovine serum albumin (BSA)-Cy5.5-SPIONs, the atherosclerotic group injected with CD40-Cy5.5-SPIONs had a stronger fluorescence signal. T2-weighted images showed that the carotid arteries of atherosclerotic mice injected with CD40-Cy5.5-SPIONs had a significant substantial T2 contrast enhancement effect. CONCLUSIONS: CD40-Cy5.5-SPIONs could potentially serve as an effective MRI/optical probe for vulnerable atherosclerotic plaques during non-invasive detection.

Integrated Analysis and Validation of Autophagy-Related Genes and Immune Infiltration in Acute Myocardial Infarction.

Background: Acute myocardial infarction (AMI) is one of the most critical conditions of coronary heart disease with many uncertainties regarding reduction of ischemia/reperfusion injury, medical treatment strategies, and other aspects. The inflammatory immune response has a bidirectional regulatory role in AMI and plays an essential role in myocardial remodeling after AMI. The purpose of our research was tantamount to explore possible mechanisms of AMI and to analyze the relationship with the immune microenvironment. Methods: We firstly analyzed the expression profile of GSE61144 and HADb to identify differentially expressed autophagy-related genes (DEARGs). Then, we performed GO, functional enrichment analysis, and constructed PPI network by Metascape. A lncRNA-miRNA-mRNA ceRNA network was built, and hub genes were extracted by Cytoscape. After that, we used CIBERSORT algorithm to estimate the proportion of immunocytes, followed by correlation analysis to find relationships between hub DEARGs and immunocyte subsets. Finally, we verified those hub genes in another dataset and cellular experiments qPCR. Results: Compared with controls, we identified 44 DEARGs and then filtered the genes of MCODE by constructing PPI network for further analysis. A total of 45 lncRNAs, 24 miRNAs, 19 mRNAs, 162 lncRNA-miRNA pairs, and 37 mRNA-miRNA pairs were used to construct a ceRNA network, and 4 hub DEARGs (BCL2, MAPK1, RAF1, and PRKAR1A) were extracted. We then estimated 5 classes of immunocytes that differed between AMI and controls. According to the results of correlation analysis, these 4 hub DEARGs may play modulatory effects in immune infiltrating cells, notably in CD8+ T cells and neutrophils. Finally, the same results were verified in GSE60993 and qPCR experiments. Conclusion: Our findings suggest that those hub DEARGs (BCL2, MAPK1, RAF1, and PRKAR1A) and immunocytes probably play functions in the progression of AMI, providing potential diagnostic markers and new perspectives for treatment of AMI.

Long-Term Prognosis of Suspected Myocarditis and Cardiomyopathy Associated with Viral Infection of the Myocardial Tissue: A Meta-Analysis of Cohort Studies.

AIM: Myocarditis and cardiomyopathy impose a substantial economic burden on society. Many studies have examined the effects of various predictors on the prognosis of these diseases, such as the left ventricular systolic function, the New York Heart Association glomerular filtration rate, the QT interval, and the presence of viruses. In the present study, we conducted a meta-analysis of cohort studies to investigate the significance of the presence of viruses in the myocardial tissue on the prognosis of these diseases. METHODS: The Embase, PubMed, and Cochrane library databases were searched for relevant literature that had been published between January 1, 1964 and August 14, 2018. The inclusion criteria were patients over 18 years of age, suspected myocarditis or dilated cardiomyopathy, accepted myocardial biopsy, and the detection of virus in the myocardial tissue. RESULTS: In total, 10 studies met the inclusion criteria. These studies included 1006 patients with suspected myocarditis or idiopathic heart disease for whom the primary endpoint was all-cause death, heart transplant, or re-hospitalization due to fatal arrhythmia and heart failure. There was no significant difference in the prognosis of virus-positive and virus-negative patients with myocarditis or dilated cardiomyopathy confirmed by endomyocardial biopsy (EMB) [hazard ratio (HR) = 1.40, 95% confidence interval (CI) = 0.93-2.12, P = 0.11]. However, virus-negative patients had a better prognosis following nonspecific treatment (HR = 1.40, 95% CI = 1.06-1.86, P = 0.02) and right ventricular biopsy (HR = 2.08, 95% CI = 1.07-4.04, P = 0.03). CONCLUSIONS: The presence of a virus did not worsen the long-term prognosis of patients with suspected myocarditis or dilated cardiomyopathy. However, virus-positive patients who did not undergo specific treatment or who underwent right ventricular biopsy did have a worse prognosis. Thus, the early diagnosis of the presence of viral infection in the myocardium will improve the prognosis of patients.