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Platelet-endothelial interactions have been linked to increased inflammatory activation and a prothrombotic state in atherosclerosis. The interaction between von Willebrand factor (vWF)-A1 domain and platelet glycoprotein (GP) Ib/IX plays a significant role in mediating the adhesion of platelets to the injured endothelium. In the present study, contrast-enhanced ultrasound (CEU) molecular imaging with microbubbles bearing the vWF-A1 domain was performed to non-invasively monitor activated platelets on the vascular endothelium in the procession of atherosclerosis. A targeted CEU contrast agent was prepared by attaching the vWF-A1 domain to the shell of microbubbles (MbA1). Rat isotype control antibody was used to produce control (Mbctrl) microbubbles. The binding of MbA1 and Mbctrl to activated platelets was assessed in in vitro flow chamber experiments. Apolipoprotein E (ApoE-/-) deficient mice were studied as a model of atherosclerosis. At 8, 16 and 32 weeks of age, CEU molecular imaging of the proximal aorta with MbA1 and Mbctrl was performed and the imaging signals from microbubbles were quantified. Atherosclerotic lesion severity and platelets on the endothelial surface were assessed by histology and immunohistochemistry. In in vitro flow chamber studies, attachment of MbA1 to activated platelets on culture dishes was significantly greater than that of Mbctrl across a range of shear stresses (P

An increasing number of studies have indicated that the abnormal expression of certain long non-coding RNAs (lncRNAs) is linked to the overall survival (OS) of patients with lung adenocarcinoma (LUAD). The aim of the present study was to establish an lncRNA signature to predict the survival of patients with LUAD. The gene expression profiles and associated clinical information of patients with LUAD were downloaded from The Cancer Genome Atlas database. The cohort was randomly sub-divided into training and verification cohorts. Univariate Cox regression analysis was performed on differentially expressed lncRNAs in the training cohort to select candidate lncRNAs closely associated with survival. Next, a risk score (RS) model consisting of 5 lncRNAs was established by multivariate Cox regression analysis on candidate lncRNAs. Using the median RS obtained from the training cohort as a cut-off point, patients were classified into high- and low-risk groups. Kaplan-Meier survival analysis revealed a significant difference in OS between high- and low-risk groups. The survival prediction ability of the 5-lncRNA signature was further tested in the verification and total cohorts. The results proved that the 5-lncRNA signature had good reliability and stability in survival prediction for patients with LUAD. The univariate Cox regression analysis for the 5-lncRNA signature in each cohort indicated that the 5-lncRNA signature was closely associated with survival. Multivariate Cox regression analysis and stratification analysis proved that the prognostic signature was an independent predictor of survival for patients with LUAD. In addition, functional enrichment analysis indicated that the 5 prognostic lncRNAs may be involved in the tumorigenesis of LUAD through cancer-associated pathways and biological processes. Taken together, the present study provided a 5-lncRNA signature that may serve as an independent survival predictor for patients with LUAD.