Open AccessDepletion of ATP and glucose in advanced human atherosclerotic plaques
Author(s) -
Matias Ekstrand,
Emma Widell,
Anna Karin Hammar,
Levent M. Akyürek,
Martin Johansson,
Björn Fagerberg,
Göran Bergström,
Malin Levin,
Per Fogelstrand,
Jan Borén
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0178877
Subject(s) - glycogen , hypoxia (environmental) , glycolysis , adenosine triphosphate , medicine , glucose transporter , glycogen storage disease , carotid endarterectomy , adenosine diphosphate , endocrinology , pathology , chemistry , biology , carotid arteries , metabolism , insulin , platelet , platelet aggregation , organic chemistry , oxygen
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.