| 1. |
- Benson, Tyler W, et al.
(författare)
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Glycoprotein VI is Critical for the Detection and Progression of Abdominal Aortic Aneurysms.
- 2023
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Ingår i: bioRxiv : the preprint server for biology.
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: A common feature in patients with abdominal aortic aneurysms (AAA) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation impacts the pathogenesis of AAA. Using RNA-sequencing, we identify that the platelet-associated transcripts are significantly enriched in the ILT compared to the adjacent aneurysm wall and healthy control aortas. We found that the platelet specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of AAA patients. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in two independent AAA patient cohorts is highly predictive of a AAA diagnosis and associates more strongly with aneurysm growth rate when compared to D-dimer in humans. Finally, intervention with the anti-GPVI antibody (J) in mice with established aneurysms blunted the progression of AAA in two independent mouse models. In conclusion, we show that levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, where none currently exist.KEY POINTS: Soluble glycoprotein VI, which is a platelet-derived blood biomarker, predicts a diagnosis of AAA, with high sensitivity and specificity in distinguishing patients with fast from slow-growing AAA.Blockade of glycoprotein VI in mice with established aneurysms reduces AAA progression and mortality, indicating therapeutic potential.
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| 2. |
- Evans, Juliet, et al.
(författare)
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Diagnostic ability of obesity measures to identify metabolic risk factors in south african women
- 2011
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Ingår i: Metabolic Syndrome and Related Disorders. - New York : Mary Ann Liebert. - 1540-4196 .- 1557-8518. ; 9:5, s. 353-360
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Tidskriftsartikel (refereegranskat)abstract
- Background: Currently, guidelines for obesity thresholds relating to metabolic risk in South African women have not been established. Therefore, the aim of the study was to investigate the level and diagnostic ability of obesity measures [waist circumference (WC), waist-to-height ratio (WHtR), and visceral adipose tissue (VAT) area] to identify black and white South African women with elevated blood pressure, dyslipidemia, and insulin resistance. Methods: Blood pressure, fasting insulin, glucose, and lipids were measured in 241 black and 188 white South African women. Receiver operator characteristic (ROC) curve analyses were performed to determine the diagnostic ability of WC, WHtR, and computer tomography (CT)-derived VAT to identify subjects above metabolic risk thresholds. The Youden index was used to calculate obesity thresholds for metabolic risk variables. Results: WC, WHtR, and VAT were significant determinants of all metabolic risk variables (P < 0.05), and differences in the ROC area under the curve (AUC) between obesity measures were small (approximate to 0.08) for all metabolic risk variables, in both ethnic groups. However, the ROC AUC vales for all obesity measures were greater in white compared to black women (P < 0.01). WC and VAT thresholds were lower in black women compared to white women, whereas WHtR thresholds varied less between ethnicities. Conclusions: Due to the cost, access, and radiation exposure, CT-derived VAT is not recommended above the use of simple anthropometric measures (WC and WHtR) for the determination of metabolic risk. Furthermore, thresholds of WHtR, due to low variability between ethnicities, may be more useful than WC for ethnic comparisons of risk.
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