Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence.Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362.

Intercellular adhesion molecule-1 (ICAM-1) has been implicated in adhesion of colorectal and pancreatic cancer cells (of the SW480 and PSN-1 line, respectively) to the peritoneal mesothelium. It has been demonstrated that ICAM-1 expression increases with senescence in some cell types, however, the significance of this phenomenon in the context of malignant dissemination remains elusive. In this report we show that the adherence of SW480 and PSN-1 cells to senescent human omentum-derived mesothelial cells (HOMCs) in vitro is greater than to early-passage cells and that the effect is mediated by ICAM-1. Senescent HOMCs display increased expression of ICAM-1 mRNA and cell surface protein. The development of this phenotype is related to increased oxidative stress in senescent cells. The augmented ICAM-1 expression in HOMCs can be reduced by culturing cells with antioxidants; in contrast, exposure of HOMCs to an oxidant, t-BHP, leads to cellular senescence and increased ICAM-1 expression. The effect is partly mediated by activation of p38 MAPK and AP-1 signaling pathways. Finally, culture of HOMCs in the presence of a strong antioxidant, PBN, significantly reduces the senescence-associated increase in SW480 and PSN-1 cancer cell binding. These results indicate that increased oxidative stress and increased expression of ICAM-1 in senescent HOMCs may facilitate peritoneal adhesion of selected colorectal and pancreatic cancers.

This study identifies polymorphisms in the HIF1A and VEGF genes as potential genetic markers that indicate the predisposition to either AAA coexisting with peripheral atherosclerosis or AAA without such lesions, suggesting the genetic heterogeneity of this disease. The HIF1A 1772T allele also seems to be a genetic risk factor that determines sensitivity to cigarette smoke exposure. Further work is needed to confirm the findings in an independent samples set and to study the functional role of studied variants in AAA.

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Background/Aims: Dysfunction of the arterial endothelial cells promotes the progression of atherosclerosis. We studied how exposure of human arterial endothelial cells to atherosclerotic serum from patients with peripheral artery disease changes the secretory activity of these cells, and whether that reaction is modified by sulodexide. Methods: Endothelial cells in in vitro culture were exposed to standard culture medium ± 100pg/mL Interleukin-1(IL-1) or to medium supplemented with 20% atherosclerotic serum. Afterwards, the expression of genes responsible for the synthesis of Interleukin-6 (IL-6), Vascular Cell Adhesion Protein-1 (VCAM-1) and Von Willebrand Factor (VWF) was evaluated, together with the secretion of these compounds. Additionally, the effect of sulodexide on these processes was studied. Results: Atherosclerotic serum stimulated the expression of IL6, VCAM-1 and VWF genes in endothelial cells, which was followed by increased secretion of these compounds by 179%, 121% and 116%, respectively. Sulodexide (0.5 LRU/mL) reduced atherosclerotic serum-induced increased expression of genes for IL-6 (-32%), VCAM-1 (-20%) and VWF (-42%), and lowered secretion of these molecules: IL-6 (-27%), VCAM-1(-27%), VWF (-25%). Sulodexide also reduced, in a dose- dependent manner, secretion of IL6 from unstimulated and stimulated with IL-1 endothelial cells. Conclusions: Atherosclerotic serum induces proinflammatory and prothrombotic phenotype in arterial endothelium, which is partially reduced by sulodexide, via inhibition of genes expression, and in consequence lower secretory activity.