| 1. |
- Celik, Selvi, et al.
(författare)
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Extracellular Vesicle-Associated TWEAK Contributes to Vascular Inflammation and Remodeling During Acute Cellular Rejection
- 2023
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Ingår i: JACC: Basic to Translational Science. - : Elsevier BV. - 2452-302X. ; 8:5, s. 439-456
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Tidskriftsartikel (refereegranskat)abstract
- Acute cellular rejection (ACR) is a leading cause of graft loss and death after heart transplantation despite effective immunosuppressive therapies. The identification of factors that impair graft vascular barrier function or promote immune cell recruitment during ACR could provide new therapeutic opportunities for the treatment of patients who receive transplants. In 2 ACR cohorts, we found the extracellular vesicle-associated cytokine TWEAK to be elevated during ACR. Vesicular TWEAK promoted expression of proinflammatory genes and the release of chemoattractant cytokines from human cardiac endothelial cells. We conclude that vesicular TWEAK is a novel target with potential therapeutic implications in ACR.
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| 2. |
- Evander, Mikael, et al.
(författare)
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Non-contact acoustic capture of microparticles from small plasma volumes.
- 2015
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Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 15:12, s. 2588-2596
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Tidskriftsartikel (refereegranskat)abstract
- Microparticles (MP) are small (100-1000 nm) membrane vesicles shed by cells as a response to activation, stress or apoptosis. Platelet-derived MP (PMP) has been shown to reflect the pathophysiological processes of a range of cardiovascular diseases and there is a potential clinical value in using PMPs as biomarkers, as well as a need to better understand the biology of these vesicles. The current method for isolating MP depends on differential centrifugation steps, which require relatively large sample volumes and have been shown to compromise the integrity and composition of the MP population. We present a novel method for rapid, non-contact capture of PMP in minute sample volumes based on a microscale acoustic standing wave technology. Capture of PMPs from plasma is shown by scanning electron microscopy and flow cytometry. Furthermore, the system is characterized with regards to plasma sample concentration and flow rate. Finally, the technique is compared to a standard differential centrifugation protocol using samples from both healthy controls and ST-elevation myocardial infarction (STEMI) patient samples. The acoustic system is shown to offer a quick and automated setup for extracting microparticles from small sample volumes with higher recovery than a standard differential centrifugation protocol.
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| 3. |
- Evander, Mikael, et al.
(författare)
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Non-contact acoustic capture of platelet-derived microparticles from small plasma volumes
- 2015
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Ingår i: MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - 9780979806483 ; , s. 469-471
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Konferensbidrag (refereegranskat)abstract
- This paper presents the characterization and optimization of acoustic capture of platelet-derived microparticles (PMPs) from human plasma. The technique is compared to a standard preparation protocol using differential centrifugation on biobank samples from patients with ST-elevation myocardial infarction (STEMI). The main advantages of this new method are the capability of rapidly capturing microvesicles from small sample volumes and the potential to extract intact vesicles for downstream processing or handling.
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| 4. |
- Gidlöf, Olof, et al.
(författare)
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Proteomic profiling of extracellular vesicles reveals additional diagnostic biomarkers for myocardial infarction compared to plasma alone
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) are submicron, membrane-enclosed particles that are released from cells in various pathophysiological states. The molecular cargo of these vesicles is considered to reflect the composition of the cell of origin, and the EV proteome is therefore a potential source of biomarkers for various diseases. Our aim was to determine whether EVs isolated from plasma provide additional diagnostic value or improved pathophysiological understanding compared to plasma alone in the context of myocardial infarction (MI). A panel of proximity extension assays (n = 92) was employed to analyze EV lysates and plasma from patients with MI (n = 60) and healthy controls (n = 22). After adjustment for multiple comparisons, a total of 11 dysregulated proteins were identified in EVs of MI patients compared to the controls (q < 0.01). Three of these proteins: chymotrypsin C (CTRC), proto-oncogene tyrosine-protein kinase SRC (SRC) and C-C motif chemokine ligand 17 (CCL17) were unaltered in the corresponding plasma samples. As biomarkers for MI, rudimentary to no evidence exists for these proteins. In a separate group of patients with varying degrees of coronary artery disease, the decrease in EV-associated (but not plasma-related) SRC levels was confirmed by ELISA. Confirmation of the presence of SRC on EVs of different sizes and cellular origins was performed with ELISA, flow cytometry and nanoparticle tracking analysis. In conclusion, the data revealed that despite a similarity in the EV and plasma proteomes, analysis of isolated EVs does indeed provide additional diagnostic information that cannot be obtained from plasma alone.
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| 5. |
- Rezeli, Melinda, et al.
(författare)
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Comparative Proteomic Analysis of Extracellular Vesicles Isolated by Acoustic Trapping or Differential Centrifugation
- 2016
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 88:17, s. 8577-8586
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (ECVs), including microparticles and exosomes, are submicrometer membrane vesicles released by diverse cell types upon activation or stress. Circulating ECVs are potential reservoirs of disease biomarkers, and the complexity of these vesicles is significantly lower compared to their source, blood plasma, which makes ECV-based biomarker studies more promising. Proteomic profiling of ECVs is important not only to discover new diagnostic or prognostic markers but also to understand their roles in biological function. In the current study, we investigated the protein composition of plasma-derived ECVs isolated by acoustic seed trapping. Additionally, the protein composition of ECVs isolated with acoustic trapping was compared to that isolated with a conventional differential centrifugation protocol. Finally, the proteome of ECVs originating from ST-elevation myocardial infarction patients was compared with that of healthy controls using label-free LC-MS quantification. The acoustic trapping platform allows rapid and automated preparation of ECVs from small sample volumes, which are therefore well-suited for biobank repositories. We found that the protein composition of trapped ECVs is very similar to that isolated by the conventional differential centrifugation method.
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