Aneurysm Formation, Growth, and Rupture: The Biology and Physics of Cerebral Aneurysms.

Cerebral aneurysms (CAs) are characterized by a pathological wall structure with internal elastic lamina and media disruption, which leads to focal weakened pouches of the arterial wall. The prevalence of unruptured CAs has been estimated to be 2%-5% in the general population. During the past few decades, the pathophysiological mechanisms behind the formation, growth, and rupture of CAs have been the focus of numerous research studies. In the present review, we have summarized the inflammatory pathways, genetics, and risk factors for the formation, growth, and rupture of CAs. In addition, we have discussed the concepts of geometric indexes, flow patterns, and fluid dynamics that govern CA development

Endothelial Cell Thrombin Receptors and PAR-2 TWO PROTEASE-ACTIVATED RECEPTORS LOCATED IN A SINGLE CELLULAR ENVIRONMENT

Human endothelial cells express thrombin receptors and PAR-2, the two known members of the family of protease-activated G protein-coupled receptors. Because previous studies have shown that the biology of the human thrombin receptor varies according to the cell in which it is expressed, we have taken advantage of the presence of both receptors in endothelial cells to examine the enabling and disabling interactions with candidate proteases likely to be encountered in and around the vascular space to compare the responses elicited by the two receptors when they are present in the same cell and to compare the mechanisms of thrombin receptor and PAR-2 clearance and replacement in a common cellular environment. Of the proteases that were tested, only trypsin activated both receptors. Cathepsin G, which disables thrombin receptors, had no effect on PAR-2, while urokinase, kallikrein, and coagulation factors IXa, Xa, XIa, and XIIa neither substantially activated nor noticeably disabled either receptor. Like thrombin receptors, activation of PAR-2 caused pertussis toxin-sensitive phospholipase C activation as well as activation of phospholipase A2, leading to the release of PGI2. Concurrent activation of both receptors caused a greater response than activation of either alone. It also abolished a subsequent response to the PAR-2 agonist peptide, SLIGRL, while only partially inhibiting the response to the agonist peptide, SFLLRN, which activates both receptors. After proteolytic or nonproteolytic activation, PAR-2, like thrombin receptors, was cleared from the endothelial cell surface and then rapidly replaced with new receptors by a process that does not require protein synthesis. Selective activation of either receptor had no effect on the clearance of the other. These results suggest that the expression of both thrombin receptors and PAR-2 on endothelial cells serves more to extend the range of proteases to which the cells can respond than it does to extend the range of potential responses. The results also show that proteases that can disable these receptors can distinguish between them, just as do most of the proteases that activate them. Finally, the residual response to SFLLRN after activation of thrombin receptors and PAR-2 raises the possibility that a third, as yet unidentified member of this family is expressed on endothelial cells, one that is activated by neither thrombin nor trypsin

Carotid Revascularization in Older Adults: A Systematic Review and Meta-Analysis

Background: Results from studies comparing carotid artery endarterectomy (CEA) with carotid artery stenting (CAS) in the elderly population are variable in the literature. The objective of this study was to investigate whether CEA or CAS is associated with a better safety profile in older adults (>80 years of age) for treatment of symptomatic and asymptomatic stenosis. Methods: A random-effects meta-analysis was performed, and the I2 statistic was used to assess heterogeneity according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Subgroup analyses were performed as needed. Results: Nine studies comprising 5955 patients were included in this meta-analysis. No differences were identified in terms of 30-day stroke (CEA: 5.8% [n = 257/4415]; CAS: 10.5% [n = 81/767]; odds ratio [OR], 0.57; 95% confidence interval [CI], 0.30–1.08; I2 = 26.1%), myocardial infarction (MI) (CEA: 1.1% [n = 4/357]; CAS: 0.5% [n = 2/355]; OR, 1.67; 95% CI, 0.37–7.46; I2 = 0%), transient ischemic attack (TIA) (CEA: 0% [n = 0/98]; CAS: 4.2% [n = 7/166]; OR, 0.28; 95% CI, 0.03–2.52; I2 = 0%), death (CEA: 1.5% [n = 8/523]; CAS: 0.9% [n = 4/431]; OR, 1.41; 95% CI, 0.43–4.58; I2 = 0%), and cranial nerve injury (CEA: 5.8% [n = 3/51]; CAS: 0% [n = 0/51]; OR, 4.74; 95% CI, 0.5–44.98; I2 =0%). A subgroup comparing CEA with transfemoral protected CAS showed that patients in the CEA group had a statistically significant lower risk of 30-day stroke (OR, 0.31; 95% CI, 0.17–0.57; I2 = 30.8%). Conclusions: This study shows that CEA is associated with a statistically significant lower risk of 30-day stroke in the elderly population compared with transfemoral CAS with distal or proximal protection. No differences were noted in the rates of periprocedural TIA, MI, death, and cranial nerve injury between CEA and CAS in the original pooled analysis. © 2019 Elsevier Inc

Thrombotic and haemorrhagic complications in patients with cerebral aneurysms treated by endovascular approach and their association with the use of antiplatelet agents: Descriptive evaluation

Objective: The protocol for optimal antiplatelet therapy to prevent thrombotic complications following brain aneurysm embolisation is not clear. Our objective is to describe the characteristics of patients presenting with thrombotic or haemorrhagic compliQ3Revista Internacional - IndexadaBS