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Increased extracellular vesicles (EVs) related to T cell-mediated inflammation and vascular function in familial hypercholesterolemia

BACKGROUND AND AIMS: OxLDL modulates innate and adaptive immunity, and extracellular vesicles (EVs) released from both non-immune and immune cells are proposed key players in atherosclerosis development. In the present study, we aimed to investigate EVs expressing markers related to adaptive immunit...

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Autores principales: Nielsen, Morten Hjuler, Bæk, Rikke, Jorgensen, Malene Moller, Mellergaard, Maiken, Handberg, Aase
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10457578/
https://www.ncbi.nlm.nih.gov/pubmed/37637934
http://dx.doi.org/10.1016/j.athplu.2023.06.004
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author Nielsen, Morten Hjuler
Bæk, Rikke
Jorgensen, Malene Moller
Mellergaard, Maiken
Handberg, Aase
author_facet Nielsen, Morten Hjuler
Bæk, Rikke
Jorgensen, Malene Moller
Mellergaard, Maiken
Handberg, Aase
author_sort Nielsen, Morten Hjuler
collection PubMed
description BACKGROUND AND AIMS: OxLDL modulates innate and adaptive immunity, and extracellular vesicles (EVs) released from both non-immune and immune cells are proposed key players in atherosclerosis development. In the present study, we aimed to investigate EVs expressing markers related to adaptive immunity-driven inflammation and endothelial activation/dysfunction in hypercholesterolemic patients. METHODS: EVs were phenotyped in thirty patients with familial hypercholesterolemia (FH) and twenty-three healthy controls using the Extracellular Vesicle (EV) Array with antibodies targeting proteins expressed on B and T cells, and endothelial cells. RESULTS: FH patients had a higher atherosclerotic burden, as determined by the mean carotid intima-media thickness (IMT) (0.64 ± 0.12 mm vs. 0.58 ± 0.07 mm; p = 0.033), higher oxLDL levels (p < 0.0001), and showed increased levels of EV-specific markers: CD9 (p = 0.017), CD63 (p = 0.045), CD81 (p = 0.003), Annexin V (p = 0.018), and EV markers related to adaptive/lymphocyte immunity: CD28 (p = 0.034), CD4 (p = 0.049), CD152 (p = 0.029), LFA-1 (p = 0.024), and endothelial function: CD62E (p = 0.032), CD144 (p = 0.018), tPA (p = 0.017), CD31 (p = 0.024). Linear regression revealed a positive relationship between carotid IMT and several of the increased markers observed within the FH group, including CD9 (β = 0.33; p = 0.022), CD63 (β = 0.35; p 225 = 0.026), CD28 (β = 0.37; p = 0.026), CD4 (β = 0.40; p = 0.025), CD152 (β = 0.41; p = 0.017), LFA-1 (β = 0.42; p = 0.014) and CD62E (β = 0.38; p = 0.024). CONCLUSION: EVs associated with adaptive immunity and endothelial dysfunction are elevated in FH patients, and several markers related to a higher atherosclerotic burden.
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spelling pubmed-104575782023-08-27 Increased extracellular vesicles (EVs) related to T cell-mediated inflammation and vascular function in familial hypercholesterolemia Nielsen, Morten Hjuler Bæk, Rikke Jorgensen, Malene Moller Mellergaard, Maiken Handberg, Aase Atheroscler Plus Full Length Article BACKGROUND AND AIMS: OxLDL modulates innate and adaptive immunity, and extracellular vesicles (EVs) released from both non-immune and immune cells are proposed key players in atherosclerosis development. In the present study, we aimed to investigate EVs expressing markers related to adaptive immunity-driven inflammation and endothelial activation/dysfunction in hypercholesterolemic patients. METHODS: EVs were phenotyped in thirty patients with familial hypercholesterolemia (FH) and twenty-three healthy controls using the Extracellular Vesicle (EV) Array with antibodies targeting proteins expressed on B and T cells, and endothelial cells. RESULTS: FH patients had a higher atherosclerotic burden, as determined by the mean carotid intima-media thickness (IMT) (0.64 ± 0.12 mm vs. 0.58 ± 0.07 mm; p = 0.033), higher oxLDL levels (p < 0.0001), and showed increased levels of EV-specific markers: CD9 (p = 0.017), CD63 (p = 0.045), CD81 (p = 0.003), Annexin V (p = 0.018), and EV markers related to adaptive/lymphocyte immunity: CD28 (p = 0.034), CD4 (p = 0.049), CD152 (p = 0.029), LFA-1 (p = 0.024), and endothelial function: CD62E (p = 0.032), CD144 (p = 0.018), tPA (p = 0.017), CD31 (p = 0.024). Linear regression revealed a positive relationship between carotid IMT and several of the increased markers observed within the FH group, including CD9 (β = 0.33; p = 0.022), CD63 (β = 0.35; p 225 = 0.026), CD28 (β = 0.37; p = 0.026), CD4 (β = 0.40; p = 0.025), CD152 (β = 0.41; p = 0.017), LFA-1 (β = 0.42; p = 0.014) and CD62E (β = 0.38; p = 0.024). CONCLUSION: EVs associated with adaptive immunity and endothelial dysfunction are elevated in FH patients, and several markers related to a higher atherosclerotic burden. Elsevier 2023-06-22 /pmc/articles/PMC10457578/ /pubmed/37637934 http://dx.doi.org/10.1016/j.athplu.2023.06.004 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Full Length Article
Nielsen, Morten Hjuler
Bæk, Rikke
Jorgensen, Malene Moller
Mellergaard, Maiken
Handberg, Aase
Increased extracellular vesicles (EVs) related to T cell-mediated inflammation and vascular function in familial hypercholesterolemia
title Increased extracellular vesicles (EVs) related to T cell-mediated inflammation and vascular function in familial hypercholesterolemia
title_full Increased extracellular vesicles (EVs) related to T cell-mediated inflammation and vascular function in familial hypercholesterolemia
title_fullStr Increased extracellular vesicles (EVs) related to T cell-mediated inflammation and vascular function in familial hypercholesterolemia
title_full_unstemmed Increased extracellular vesicles (EVs) related to T cell-mediated inflammation and vascular function in familial hypercholesterolemia
title_short Increased extracellular vesicles (EVs) related to T cell-mediated inflammation and vascular function in familial hypercholesterolemia
title_sort increased extracellular vesicles (evs) related to t cell-mediated inflammation and vascular function in familial hypercholesterolemia
topic Full Length Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10457578/
https://www.ncbi.nlm.nih.gov/pubmed/37637934
http://dx.doi.org/10.1016/j.athplu.2023.06.004
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