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Depletion of ATP and glucose in advanced human atherosclerotic plaques

Ekstrand, Matias; Widell, Emma; Hammar, Anna; Akyürek, Levent M.; Johansson, Martin LU ; Fagerberg, Björn; Bergström, Göran; Levin, Malin C; Fogelstrand, Per and Borén, Jan, et al. (2017) In PLoS ONE 12(6). p.1-10
Abstract

Objective: Severe hypoxia develops close to the necrotic core of advanced human atherosclerotic plaques, but the energy metabolic consequences of this hypoxia are not known. In animal models, plaque hypoxia is also associated with depletion of glucose and ATP. ATP depletion may impair healing of plaques and promote necrotic core expansion. To investigate if ATP depletion is present in human plaques, we analyzed the distribution of energy metabolites (ATP, glucose, glycogen and lactate) in intermediate and advanced human plaques. Approach and results: Snap frozen carotid endarterectomies from 6 symptomatic patients were analyzed. Each endarterectomy included a large plaque ranging from the common carotid artery (CCA) to the internal... (More)

Objective: Severe hypoxia develops close to the necrotic core of advanced human atherosclerotic plaques, but the energy metabolic consequences of this hypoxia are not known. In animal models, plaque hypoxia is also associated with depletion of glucose and ATP. ATP depletion may impair healing of plaques and promote necrotic core expansion. To investigate if ATP depletion is present in human plaques, we analyzed the distribution of energy metabolites (ATP, glucose, glycogen and lactate) in intermediate and advanced human plaques. Approach and results: Snap frozen carotid endarterectomies from 6 symptomatic patients were analyzed. Each endarterectomy included a large plaque ranging from the common carotid artery (CCA) to the internal carotid artery (ICA). ATP, glucose, and glycogen concentrations were lower in advanced (ICA) compared to intermediate plaques (CCA), whereas lactate concentrations were higher. The lowest concentrations of ATP, glucose and glycogen were detected in the perinecrotic zone of advanced plaques. Conclusions: Our study demonstrates severe ATP depletion and glucose deficiency in the perinecrotic zone of human advanced atherosclerotic plaques. ATP depletion may impair healing of plaques and promote disease progression.

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published
subject
in
PLoS ONE
volume
12
issue
6
pages
1 - 10
publisher
Public Library of Science
external identifiers
  • scopus:85020007453
  • wos:000402611800131
ISSN
1932-6203
DOI
10.1371/journal.pone.0178877
language
English
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yes
id
913aef8a-91d6-4044-8d09-3ed189583365
date added to LUP
2017-06-19 10:55:37
date last changed
2018-04-29 04:39:53
@article{913aef8a-91d6-4044-8d09-3ed189583365,
  abstract     = {<p>Objective: Severe hypoxia develops close to the necrotic core of advanced human atherosclerotic plaques, but the energy metabolic consequences of this hypoxia are not known. In animal models, plaque hypoxia is also associated with depletion of glucose and ATP. ATP depletion may impair healing of plaques and promote necrotic core expansion. To investigate if ATP depletion is present in human plaques, we analyzed the distribution of energy metabolites (ATP, glucose, glycogen and lactate) in intermediate and advanced human plaques. Approach and results: Snap frozen carotid endarterectomies from 6 symptomatic patients were analyzed. Each endarterectomy included a large plaque ranging from the common carotid artery (CCA) to the internal carotid artery (ICA). ATP, glucose, and glycogen concentrations were lower in advanced (ICA) compared to intermediate plaques (CCA), whereas lactate concentrations were higher. The lowest concentrations of ATP, glucose and glycogen were detected in the perinecrotic zone of advanced plaques. Conclusions: Our study demonstrates severe ATP depletion and glucose deficiency in the perinecrotic zone of human advanced atherosclerotic plaques. ATP depletion may impair healing of plaques and promote disease progression.</p>},
  articleno    = {e0178877},
  author       = {Ekstrand, Matias and Widell, Emma and Hammar, Anna and Akyürek, Levent M. and Johansson, Martin and Fagerberg, Björn and Bergström, Göran and Levin, Malin C and Fogelstrand, Per and Borén, Jan and Levin, Max},
  issn         = {1932-6203},
  language     = {eng},
  month        = {06},
  number       = {6},
  pages        = {1--10},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Depletion of ATP and glucose in advanced human atherosclerotic plaques},
  url          = {http://dx.doi.org/10.1371/journal.pone.0178877},
  volume       = {12},
  year         = {2017},
}