ATP Inside and Out: Understanding Atherosclerosis Through Energy Metabolism and Purinergic Signaling

Abstract

Adenosine triphosphate (ATP) is well known as the major intracellular energy carrier. It also functions as a potent extracellular signaling molecule. In atherosclerosis, both intracellular and extracellular ATP have been increasingly implicated in the disease pathophysiology. The intracellular ATP levels are closely regulated by the balance among the metabolic pathways, including glycolysis and oxidative phosphorylation (OXPHOS), and they play diverse and cell type-specific roles in atherosclerotic plaques. In contrast, the extracellular ATP released from these cells binds to purinergic P2 receptors and activates downstream signaling cascades primarily in an autocrine or paracrine manner, thereby regulating various cellular functions during disease progression. These two contrasting ATP-associated pathways are involved in a wide range of atherosclerosis-related processes including inflammation, vascular tone and barrier function, cell proliferation, migration and differentiation, and calcification, some of which are shared or highly context-dependent. This review summarizes the fundamental aspects of ATP biology, discusses the current approaches for measuring ATP concentrations in atherosclerotic plaques, and highlights the functions of intra- and extracellular ATP in major atherosclerosis-related cell types, including endothelial cells, macrophages and vascular smooth muscle cells (VSMCs), to clarify these intricately intertwined pathophysiological processes. Finally, this overview provides insights into the current challenges in ATP biology research and outlines therapeutic opportunities targeting intra- or extracellular ATP in atherosclerotic disease.

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BibTeX RIS

BibTeX

@article{baba2026inside,
  title = {{ATP Inside and Out: Understanding Atherosclerosis Through Energy Metabolism and Purinergic Signaling}},
  author = {Osamu Baba and Koh Ono},
  journal = {Journal of Atherosclerosis and Thrombosis},
  year = {2026},
  month = oct,
  doi = {10.5551/jat.rv22054},
  url = {https://www.jstage.jst.go.jp/article/jat/33/10/33_RV22054/_article},
  note = {CC BY-NC-SA},
}

RIS

TY  - JOUR
TI  - ATP Inside and Out: Understanding Atherosclerosis Through Energy Metabolism and Purinergic Signaling
AU  - Osamu Baba
AU  - Koh Ono
PY  - 2026
DA  - 2026/10/01
JO  - Journal of Atherosclerosis and Thrombosis
DO  - 10.5551/jat.rv22054
UR  - https://www.jstage.jst.go.jp/article/jat/33/10/33_RV22054/_article
AB  - Adenosine triphosphate (ATP) is well known as the major intracellular energy carrier. It also functions as a potent extracellular signaling molecule. In atherosclerosis, both intracellular and extracellular ATP have been increasingly implicated in the disease pathophysiology. The intracellular ATP levels are closely regulated by the balance among the metabolic pathways, including glycolysis and oxidative phosphorylation (OXPHOS), and they play diverse and cell type-specific roles in atherosclerotic plaques. In contrast, the extracellular ATP released from these cells binds to purinergic P2 receptors and activates downstream signaling cascades primarily in an autocrine or paracrine manner, thereby regulating various cellular functions during disease progression. These two contrasting ATP-associated pathways are involved in a wide range of atherosclerosis-related processes including inflammation, vascular tone and barrier function, cell proliferation, migration and differentiation, and calcification, some of which are shared or highly context-dependent. This review summarizes the fundamental aspects of ATP biology, discusses the current approaches for measuring ATP concentrations in atherosclerotic plaques, and highlights the functions of intra- and extracellular ATP in major atherosclerosis-related cell types, including endothelial cells, macrophages and vascular smooth muscle cells (VSMCs), to clarify these intricately intertwined pathophysiological processes. Finally, this overview provides insights into the current challenges in ATP biology research and outlines therapeutic opportunities targeting intra- or extracellular ATP in atherosclerotic disease.
SN  - 1880-3873
SN  - 1340-3478
ER  -

Abstract

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