Objective-Lipids are central to the development of atherosclerotic plaques. Specifically, which lipids are culprits remains controversial, and promising targets have failed in clinical studies. Sphingolipids are bioactive lipids present in atherosclerotic plaques, and they have been suggested to have both proatherogenic and antiatherogenic. However, the biological effects of these lipids remain unknown in the human atherosclerotic plaque. The aim of this study was to assess plaque levels of sphingolipids and investigate their potential association with and contribution to plaque vulnerability. Approach and Results-Glucosylceramide, lactosylceramide, ceramide, dihydroceramide, sphingomyelin, and sphingosine-1-phosphate were analyzed in homogenates from 200 human carotid plaques using mass spectrometry. Inflammatory activity was determined by analyzing plaque levels of cytokines and plaque histology. Caspase-3 was analyzed by ELISA technique. Expression of regulatory enzymes was analyzed with RNA sequencing. Human coronary artery smooth muscle cells were used to analyze the potential role of the 6 sphingolipids as inducers of plaque inflammation and cellular apoptosis in vitro. All sphingolipids were increased in plaques associated with symptoms and correlated with inflammatory cytokines. All sphingolipids, except sphingosine-1-phosphate, also correlated with histological markers of plaque instability. Lactosylceramide, ceramide, sphingomyelin, and sphingosine-1-phosphate correlated with caspase-3 activity. In vitro experiments revealed that glucosylceramide, lactosylceramide, and ceramide induced cellular apoptosis. All analyzed sphingolipids induced an inflammatory response in human coronary artery smooth muscle cells. Conclusions-This

Combined reflux in more than one pelvic vein is common. In these cases, isolated treatment of ovarian veins or conservative treatment is associated with a poor midterm clinical outcome. A clinical improvement was achieved only in patients with isolated ovarian vein incompetence.

In this prospective study MRV showed high sensitivity in the evaluation of patients with suspected PVC. Routine use of this diagnostic method requires further studies in larger patient cohorts.

Background When the lectinlike oxidized low‐density lipoprotein (ox LDL) receptor‐1 ( LOX ‐1), a scavenger receptor for ox LDL , binds ox LDL , processes leading to endothelial dysfunction and inflammation are promoted. We aimed to study release mechanisms of LOX ‐1 and how circulating levels of soluble LOX ‐1 ( sLOX ‐1) relate to plaque inflammation and future risk for ischemic stroke. Methods and Results Endothelial cells and leukocytes were used to study release of sLOX ‐1. Plasma levels of sLOX ‐1 were determined in 4703 participants in the Malmö Diet and Cancer cohort. Incidence of ischemic stroke was monitored. For 202 patients undergoing carotid endarterectomy, levels of sLOX ‐1 were analyzed in plasma and plaque homogenates and related to plaque inflammation factors. Endothelial cells released sLOX ‐1 when exposed to ox LDL . A total of 257 subjects experienced stroke during a mean follow‐up of 16.5 years. Subjects in the highest tertile of sLOX ‐1 had a stroke hazard ratio of 1.75 (95% CI, 1.28–2.39) compared with those in the lowest tertile after adjusting for age and sex. The patients undergoing carotid endarterectomy had a significant association between plasma sLOX ‐1 and the plaque content of sLOX ‐1 ( r =0.209, P =0.004). Plaques with high levels of sLOX ‐1 had more ox LDL , proinflammatory cytokines, and matrix metalloproteinases. Conclusions Our findings demonstrate that ox LDL induces the release of sLOX ‐1 from endothelial cells and that circulating levels of sLOX ‐1 correlate with carotid plaque inflammation and risk for ischemic stroke. These observations provide clinical support to experimental studies implicating LOX ‐1 in atherosclerosis and its possible role as target for cardiovascular intervention.

Background: Surgical-site infection (SSI) after groin incisions for arterial surgery is common and may lead to amputation or death. Incisional negative pressure wound therapy (NPWT) dressings have been suggested to reduce SSIs. The aim of this systematic review with meta-analysis was to assess the effects of incisional NPWT on the incidence of SSI in closed groin incisions after arterial surgery.Methods: A study protocol for this systematic review of RCTs was published in Prospero (CRD42018090298) a priori, with predefined search, inclusion and exclusion criteria. The records generated by the systematic research were screened for relevance by title and abstract and in full text by two of the authors independently. The selected articles were rated for bias according to the Cochrane risk-of-bias tool.Results: Among 1567 records generated by the search, seven RCTs were identified, including 1049 incisions. Meta-analysis showed a reduction in SSI with incisional NPWT (odds ratio (OR) 0⋅35, 95 per cent c.i. 0⋅24 to 0⋅50; P < 0⋅001). The heterogeneity between the included studies was low (I 2 = 0 per cent). The quality of evidence was graded as moderate. Two studies had multiple domains in the Cochrane risk-of-bias tool rated as high risk of bias. A subgroup meta-analysis of three studies of lower limb revascularization procedures only (363 incisions) demonstrated a similar reduction in SSI (OR 0⋅37, 0⋅22 to 0⋅63; P < 0⋅001; I 2 = 0 per cent).Conclusion: Incisional NPWT after groin incisions for arterial surgery reduced the incidence of SSI compared with standard wound dressings. The risk of bias highlighted the need for a high-quality RCT with cost-effectiveness analysis.

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Several large-scale genome-wide association studies have identified single-nucleotide polymorphisms in the genomic region of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 repeats (ADAMTS)-7 and associations to coronary artery disease. Experimental studies have provided evidence for a functional role of ADAMTS-7 in both injury-induced vascular neointima formation and development of atherosclerotic lesions. However, whether ADAMTS-7 is associated with a specific plaque phenotype in humans has not been investigated. Carotid plaques (n = 206) from patients with and without cerebrovascular symptoms were analyzed for expression of ADAMTS-7 by immunohistochemistry and correlated to components associated with plaque vulnerability. Plaques from symptomatic patients showed increased levels of ADAMTS-7 compared with lesions from asymptomatic patients. High levels of ADAMTS-7 correlated with high levels of CD68-staining and lipid content, but with low smooth muscle cell and collagen content, which together are characteristics of a vulnerable plaque phenotype. ADAMTS-7 levels above median were associated with increased risk for postoperative cardiovascular events. Our data show that ADAMTS-7 is associated with a vulnerable plaque phenotype in human carotid lesions. These data support previous observations of a potential proatherogenic role of ADAMTS-7.Several large-scale genome-wide association studies (GWAS) have identified SNPs in the genomic region of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 repeats (ADAMTS)-7 and associations to coronary artery disease (CAD) 1-3 . ADAMTS-7 is a proteolytic enzyme and its best characterized substrate is the cartilage oligomeric protein (COMP) also known as thromobospondin-5 4 . Previous studies have focused on the role of ADAMTS-7 in cartilage degradation, and recently ADAMTS-7 was shown to enhance both osteoarthritis and collagen-induced arthritis in mice 5,6 . In a rodent model of vascular disease, ADAMTS-7 has been implicated in restenosis 7 , which was recently confirmed in two studies using ADAMTS-7-deficient mice 8,9 . The role of ADAMTS-7 in neointima formation is mediated via increased smooth muscle cell (SMC) migration by degradation of COMP and via impaired re-endothelialization 7, 9 . In agreement with this, the SNP (identified by GWAS) rs3825807 (A to G), leading to a Ser-to-Pro substitution in the prodomain of ADAMTS-7, reduces cleavage of the prodomain of ADAMTS-7, SMC-mediated COMP degradation, and SMC migration 10 . In addition to its role in restenosis, a recent study showed that ADAMTS-7-deficiency significantly reduces atherosclerotic lesion formation in both ApoE −/− and LDLr −/− mice 8 . In cultured SMCs, ADAMTS-7 expression is up-regulated by inflammatory cytokines such as TNF-α, interleukin-1β, reactive oxygen species (H 2 O 2 ), and platelet-derived growth factor-BB, whereas the anti-inflammatory cytokine transforming growth factor-β reduces ADAMTS-7 expression 7,9 . ADAMTS-7 is also expressed in monocytes/macrophages, and int...

Background: Galectin-3 (Gal-3) has been suggested to have both pro- and anti-atherogenic properties. High plasma Gal-3 levels are associated with increased risk for cardiovascular (CV) death. However, it has so far not been investigated if plasma Gal-3 levels can predict the risk for future stroke in patients suffering from carotid atherosclerosis. The aim of this study was to investigate whether Gal-3 could be used as a marker to predict postoperative cerebrovascular ischemic events among patients who underwent carotid endarterectomy (CEA). Methods: Plasma samples were obtained from 558 CEA patients and Gal-3 levels were analyzed by the proximity extension assay technique. The Swedish national in-patient health register was used to identify postoperative cerebrovascular events during the follow-up period (42.6 ± 26.2 months). Results: Plasma Gal-3 was increased in patients treated for a symptomatic carotid stenosis (p = 0.013). Patients with Gal-3 levels above the median value had an increased incidence of stroke as shown by Kaplan-Meier curves of event-free survival (p = 0.007). Gal-3 was a predictor of postoperative stroke among women (hazard ratio 15.1, 95% CI 1.3-172.2; p = 0.028) even after correction for traditional CV risk factors. Conclusions: This study is the first to show that increased plasma levels of Gal-3 can help in predicting the occurrence of postoperative strokes among female subjects who undergo CEA, independently of traditional risk factors for cerebrovascular disease. This finding suggests that Gal-3 could be used as a marker to identify patients in need of intensified postoperative medical care.