Serum is an abundant and accessible source of circulating extracellular vesicles (EVs). Serum-EV (sEV) pro-angiogenic capability and mechanisms are herein analyzed using an in vitro assay which predicts sEV angiogenic potential in vivo. Effective sEVs (e-sEVs) also improved vascular remodeling and prevented muscle damage in a mouse model of acute hind limb ischemia. e-sEV angiogenic proteomic and transcriptomic analyses show a positive correlation with matrix-metalloproteinase activation and extracellular matrix organization, cytokine and chemokine signaling pathways, Insulin-like Growth Factor and platelet pathways, and Vascular Endothelial Growth Factor signaling. A discrete gene signature, which highlights differences in e-sEV and ineffective-EV biological activity, was identified using gene ontology (GO) functional analysis. An enrichment of genes associated with the Transforming Growth Factor beta 1 (TGFβ1) signaling cascade is associated with e-sEV administration but not with ineffective-EVs. Chromatin immunoprecipitation analysis on the inhibitor of DNA binding I (ID1) promoter region, and the knock-down of small mother against decapentaplegic (SMAD)1–5 proteins confirmed GO functional analyses. This study demonstrates sEV pro-angiogenic activity, validates a simple, sEV pro-angiogenic assay which predicts their biological activity in vivo, and identifies the TGFβ1 cascade as a relevant mediator. We propose serum as a readily available source of EVs for therapeutic purposes.

Growing evidence suggests that small vesicles actively released from cells may encapsulate transcriptional regulators and RNA molecules. Their ability to interact with neighbouring cells and/or with distant cells through biological fluids, makes them a medium through which intercellular exchange of information can happen. Recently, membrane vesicles, which include exosomes and microvesicles, gained a place amongst the vast group of angiogenic mediators. In the present review we discuss the potential relevance of these vesicles in physiological and pathological situations of angiogenesis as well as their mechanism of action.

Objective: The aim of this study was to evaluate the incidence of acute kidney injury (AKI) after open and endovascular abdominal aortic aneurysm repair according to the Aneurysm Renal Injury Score classification. Methods: We retrospectively evaluated 431 patients undergoing elective open aortic repair (OAR; n [ 285) or endovascular repair (n [ 146) for infrarenal aortic aneurysm. All data regarding preoperative and postoperative serum creatinine concentrations and postoperative outcomes were assessed. Univariate and multivariate logistic regression models investigated the association between AKI and different risk factors and complications. Results: The incidence of AKI was significantly higher after OAR (26.3% vs 5.5%; P < .001). A significant share of patients who experienced AKI were restored to preoperative renal function at discharge (62.5% vs 77.5% in the endovascular and OAR groups, respectively; P [ .37). Preoperative serum creatinine concentration was significantly higher in those patients who further developed AKI (1.25 vs 1.04 mg/dL; P < .001). At the multivariate analysis, AKI was significantly associated with current smoking (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.19-3.52; P [ .01), hypertension (OR, 2.46; 95% CI, 1.21-4.3; P [ .01), chronic renal disease (OR, 2.53; 95% CI, 1.42-4.53; P < .001), OAR (OR, 7.3; 95% CI, 3.25-16.42; P < .001), and arrhythmias (OR, 3.16; 95% CI, 1.09-9.13; P [ .03). AKI stage did not affect postoperative outcomes, except for a longer hospital stay in patients in stage 2 and stage 3 compared with stage 1. Conclusions: AKI is a common but often reversible complication, especially after OAR. There is an urgent need of a common classification for AKI after aortic surgery. New diagnostic markers for AKI should be evaluated in large-scale studies to assess their reliability. (J Vasc Surg 2016;64:928-33.)

Contrast-enhanced ultrasound (CEUS) has recently become one of the most versatile and powerful diagnostic tools in vascular surgery. One of the most interesting fields of application of this technique is the study of the carotid atherosclerotic plaque vascularization and its correlation with neurological symptoms (transient ischemic attack, minor stroke, and major stroke) and with the characteristics of the “vulnerable plaque” (surface ulceration, hypoechoic plaques, intraplaque hemorrhage, thinner fibrous cap, and carotid plaque neovascularization at histopathological analysis of the sample after surgical removal). The purpose of this review is to collect all the original studies available in literature (24 studies with 1356 patients enrolled) and to discuss the state of the art, limits, and future perspectives of CEUS analysis. The results of this work confirm the reliability of this imaging study for the detection of plaques with high risk of embolization; however, a shared, user-friendly protocol of imaging analysis is not available yet. The definition of this operative protocol becomes mandatory in order to compare results from different centers and to validate a cerebrovascular risk stratification of the carotid atherosclerotic lesions evaluated with CEUS.