BACKGROUND: Symptomatic carotid disease due to thromboembolism has been associated with acute plaque instability and intraplaque haemorrhage. These features may be influenced by the fragility and position of plaque neovessels. The purpose of this study was, therefore, to determine whether any association existed between neovessel density, position, morphology and thromboembolic sequelae. METHODS: Carotid endarterectomy (CEA) samples were collected from 15 asymptomatic patients with greater than 80 per cent stenosis and from 13 patients with greater than 80 per cent stenosis and symptoms within 30 days of CEA. Groups were matched for sex, age, risk factors and plaque size. Samples were stained with haematoxylin and eosin, and Van Gieson stains. An endothelial-specific antibody to CD31 was used for immunohistochemistry. Plaques were assessed for histological characteristics while neovessels were counted and characterized by size, site and shape. RESULTS: There were more neovessels in plaques (P < 0.00001) and fibrous caps (P < 0.0001) from symptomatic than asymptomatic patients. Symptomatic plaque neovessels were larger in size (P< 0.004) and more irregular in shape. There was a significant increase in plaque necrosis and rupture in symptomatic plaques. Plaque haemorrhage and rupture were associated with more neovessels within the plaque (P < 0.02, P < 0. 001) and fibrous cap (P < 0.05, P < 0.004). Patients with preoperative or intraoperative embolization had more plaque and fibrous cap neovessels (P < 0.03, P < 0.001). CONCLUSION: Symptomatic carotid disease is associated with increased neovascularization within the atherosclerotic plaque and fibrous cap; these vessels appear larger in size, more irregular in shape and may contribute to plaque instability and onset of thromboembolic events.
Summary
Formins are actin assembly factors that act in a variety of actin-based processes. The conserved formin homology 2 (FH2) domain promotes filament nucleation and influences elongation via interaction with the barbed end. FMNL3 is a formin that induces assembly of filopodia but whose FH2 domain is a poor nucleator. The 3.4 Å structure of an FMNL3 FH2 dimer in complex with tetramethylrhodamine-actin uncovers details of formin-regulated actin elongation. We observe distinct FH2-actin binding regions; interactions in the knob and coiled-coil subdomains are necessary for actin binding while those in the lasso/post interface are important for the stepping mechanism. Biochemical and cellular experiments test the importance of individual residues for function. This structure provides details for FH2 mediated filament elongation via processive capping and supports a model in which C-terminal non-FH2 residues of FMNL3 are required to stabilize the filament nucleus.
This study demonstrated that abdominal aortic aneurysms are associated with a marked angiogenic response, which is related to the degree of inflammation within the aortic wall. It is hypothesised that anti-angiogenic agents may play a role in the medical management of aortic aneurysmal disease.
Germline mutations in BRCA1 are responsible for most cases of inherited breast and ovarian cancer. However, the function of the BRCA1 protein has remained elusive. We now show that BRCA1 encodes a 190-kD protein with sequence homology and biochemical analogy to the granin protein family. Interestingly, BRCA2 also includes a motif similar to the granin consensus at the C terminus of the protein. Both BRCA1 and the granins localize to secretory vesicles, are secreted by a regulated pathway, are post-translationally glycosylated and are responsive to hormones. As a regulated secretory protein, BRCA1 appears to function by a mechanism not previously described for tumour suppressor gene products.
Severe complications after bilateral IIA embolization are uncommon. Although buttock/thigh claudication occurs in around 30% of patients soon after the procedure, this resolves in the majority after 1 year. There is no obvious benefit for sequential versus simultaneous IIA embolization in our series. Occlusion of the proximal IIA trunk is associated with reduced complications compared with occlusion of the distal IIA.
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