Depletion of ATP and glucose in advanced human atherosclerotic plaques.

Matias Ekstrand,Anna Hammar,Björn Fagerberg,Levent M Akyürek,Martin Johansson,Max Levin,Per Fogelstrand,Malin C Levin,Jan Borén,Göran Bergström,Emma Widell

doi:10.1371/journal.pone.0178877

Abstract

ObjectiveSevere 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 resultsSnap 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.ConclusionsOur 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.

Highlights

Cells need oxygen and nutrients to produce ATP required for ion pumps, migration and intracellular metabolism
Our study demonstrates severe ATP depletion and glucose deficiency in the perinecrotic zone of human advanced atherosclerotic plaques
Our results demonstrate severe cellular ATP depletion and lack of glucose in advanced human plaques, in particular close to the necrotic core

Summary

Introduction

Cells need oxygen and nutrients to produce ATP required for ion pumps, migration and intracellular metabolism. Oxygen and nutrients are supplied via diffusion from. ATP depletion in human atherosclerotic plaques luminal blood and vasa vasorum [1, 2]. In atherosclerosis-prone large and medium-sized arteries, diffusion distances are long. Diffusion distances increase further as the intima grows thicker. The energy metabolic demand increase due to accumulation of macrophage foam cells with high oxygen and glucose consumption [3]. Lack of oxygen and nutrients may develop deep in plaques promoting energy (ATP) depletion

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Results

Conclusion