Diverse ultrastructural landscape of atherosclerotic endothelium
Kluza, Ewelina ; Beldman, Thijs J. ; Shami, Annelie LU
; Scholl, Edwin R.
; Malinova, Tsveta S.
; Grootemaat, Anita E.
; van der Wel, Nicole N.
; Gonçalves, Isabel
LU
; Huveneers, Stephan
and Mulder, Willem J.M.
, et al.
(2021)
In Atherosclerosis
339.
p.35-45
- Abstract
Background and aims: The endothelium plays a major role in atherosclerosis, yet the endothelial plaque surface is a largely uncharted territory. Here we hypothesize that atherosclerosis-driven remodeling of the endothelium is a dynamic process, involving both damaging and regenerative mechanisms. Methods: Using scanning electron microscopy (SEM) and immuno-SEM, we studied endothelial junction ultrastructure, endothelial openings and immune cell-endothelium interactions in eight apoe−/− mice and two human carotid plaques. Results: The surface of early mouse plaques (n = 11) displayed a broad range of morphological alterations, including junctional disruptions and large transcellular endothelial pores with the average diameter... (More)
Background and aims: The endothelium plays a major role in atherosclerosis, yet the endothelial plaque surface is a largely uncharted territory. Here we hypothesize that atherosclerosis-driven remodeling of the endothelium is a dynamic process, involving both damaging and regenerative mechanisms. Methods: Using scanning electron microscopy (SEM) and immuno-SEM, we studied endothelial junction ultrastructure, endothelial openings and immune cell-endothelium interactions in eight apoe−/− mice and two human carotid plaques. Results: The surface of early mouse plaques (n = 11) displayed a broad range of morphological alterations, including junctional disruptions and large transcellular endothelial pores with the average diameter between 0.6 and 3 μm. The shoulder region of advanced atherosclerotic lesions (n = 7) had a more aggravated morphology with 8 μm-size paracellular openings at two-fold higher density. In contrast, the central apical surface of advanced plaques, i.e., the plaque body (n = 7), displayed endothelial normalization, as shown by a significantly higher frequency of intact endothelial junctions and a lower incidence of paracellular pores. This normalized endothelial phenotype correlated with low immune cell density (only 5 cells/mm2). The human carotid plaque surface (n = 2) displayed both well-organized and disrupted endothelium with similar features as described above. In addition, they were accompanied by extensive thrombotic areas. Conclusions: Our study unveils the spectrum of endothelial abnormalities associated with the development of atherosclerosis. These were highly abundant in early lesions and in the shoulder region of advanced plaques, while normalized at the advanced plaque's body. Similar endothelial features were observed in human atherosclerotic plaques, underlining the versatility of endothelial transformations in atherosclerosis.
(Less)
- author
- Kluza, Ewelina
; Beldman, Thijs J.
; Shami, Annelie
LU
; Scholl, Edwin R.
; Malinova, Tsveta S.
; Grootemaat, Anita E.
; van der Wel, Nicole N.
; Gonçalves, Isabel
LU
; Huveneers, Stephan
and Mulder, Willem J.M.
, et al. (More)
- Kluza, Ewelina
; Beldman, Thijs J.
; Shami, Annelie
LU
; Scholl, Edwin R.
; Malinova, Tsveta S.
; Grootemaat, Anita E.
; van der Wel, Nicole N.
; Gonçalves, Isabel
LU
; Huveneers, Stephan
; Mulder, Willem J.M.
and Lutgens, Esther
(Less)
- organization
- publishing date
- 2021-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Atherosclerosis, Endothelial junctions, Endothelial permeability, Endothelium, Scanning electron microscopy
- in
- Atherosclerosis
- volume
- 339
- pages
- 11 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:34847419
- scopus:85119987822
- ISSN
- 0021-9150
- DOI
- 10.1016/j.atherosclerosis.2021.11.017
- language
- English
- LU publication?
- yes
- id
- 6515f878-a21b-432e-981a-304f38b19800
- date added to LUP
- 2021-12-15 11:45:38
- date last changed
- 2024-04-06 15:18:48
@article{6515f878-a21b-432e-981a-304f38b19800,
abstract = {{<p>Background and aims: The endothelium plays a major role in atherosclerosis, yet the endothelial plaque surface is a largely uncharted territory. Here we hypothesize that atherosclerosis-driven remodeling of the endothelium is a dynamic process, involving both damaging and regenerative mechanisms. Methods: Using scanning electron microscopy (SEM) and immuno-SEM, we studied endothelial junction ultrastructure, endothelial openings and immune cell-endothelium interactions in eight apoe<sup>−/−</sup> mice and two human carotid plaques. Results: The surface of early mouse plaques (n = 11) displayed a broad range of morphological alterations, including junctional disruptions and large transcellular endothelial pores with the average diameter between 0.6 and 3 μm. The shoulder region of advanced atherosclerotic lesions (n = 7) had a more aggravated morphology with 8 μm-size paracellular openings at two-fold higher density. In contrast, the central apical surface of advanced plaques, i.e., the plaque body (n = 7), displayed endothelial normalization, as shown by a significantly higher frequency of intact endothelial junctions and a lower incidence of paracellular pores. This normalized endothelial phenotype correlated with low immune cell density (only 5 cells/mm<sup>2</sup>). The human carotid plaque surface (n = 2) displayed both well-organized and disrupted endothelium with similar features as described above. In addition, they were accompanied by extensive thrombotic areas. Conclusions: Our study unveils the spectrum of endothelial abnormalities associated with the development of atherosclerosis. These were highly abundant in early lesions and in the shoulder region of advanced plaques, while normalized at the advanced plaque's body. Similar endothelial features were observed in human atherosclerotic plaques, underlining the versatility of endothelial transformations in atherosclerosis.</p>}},
author = {{Kluza, Ewelina and Beldman, Thijs J. and Shami, Annelie and Scholl, Edwin R. and Malinova, Tsveta S. and Grootemaat, Anita E. and van der Wel, Nicole N. and Gonçalves, Isabel and Huveneers, Stephan and Mulder, Willem J.M. and Lutgens, Esther}},
issn = {{0021-9150}},
keywords = {{Atherosclerosis; Endothelial junctions; Endothelial permeability; Endothelium; Scanning electron microscopy}},
language = {{eng}},
pages = {{35--45}},
publisher = {{Elsevier}},
series = {{Atherosclerosis}},
title = {{Diverse ultrastructural landscape of atherosclerotic endothelium}},
url = {{http://dx.doi.org/10.1016/j.atherosclerosis.2021.11.017}},
doi = {{10.1016/j.atherosclerosis.2021.11.017}},
volume = {{339}},
year = {{2021}},
}