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Peer-reviewedCC BY-NCJournal of inflammation research

Extracellular ATP Signaling as a Proposed Mechanistic Link to Cellular Senescence in Cardiovascular Diseases.

  • Xuesong Liu1
  • Jingjing Zhang2,3,4
  • Jingjing Lu5
  • Zhihao Hu5
  • Huiting Wei5
  • Linzhu Li5
  • Yufei Yang6
  • Jinhai Liu7
  • Zhaoyu Li8
  • Haoling Zhang9
  • Wangzheqi Zhang10
10 affiliations
  1. 1School of Basic Medical Sciences, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, People's Republic of China.
  2. 2Yunnan Key Laboratory of Innovative Diagnosis and Treatment of Circulatory Diseases, Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, Affiliated Cardiovascular Hospital of Kunming Medical University, Kunming, Yunnan, 650000, People's Republic of China.
  3. 3Yunnan Provincial Cardiovascular Clinical Medical Center, Kunming, Yunnan, 650000, People's Republic of China.
  4. 4Yunnan Provincial Cardiovascular Clinical Medical Research Center, Kunming, Yunnan, 650000, People's Republic of China.
  5. 5School of Clinical Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, People's Republic of China.
  6. 6School of Public Health, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, People's Republic of China.
  7. 7Medical School, Hubei Minzu University, Enshi, Hubei, 445000, People's Republic of China.
  8. 8College of Acupuncture-Moxibustion and Tuina, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, People's Republic of China.
  9. 9Department of Biomedical Sciences, Pusat Kanser Tun Abdullah Ahmad Badawi, Universiti Sains Malaysia, Kepala Batas, Pulau Pinang, 13200, Malaysia.
  10. 10School of Anesthesiology, Naval Medical University, Shanghai, 200433, People's Republic of China.
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Abstract

Cellular senescence represents a critical pathological process involved in the progression of cardiovascular diseases (CVDs). Senescent endothelial cells, cardiomyocytes, vascular smooth muscle cells (VSMCs), and immune cells can promote inflammatory responses, oxidative stress, extracellular matrix (ECM) degradation, and fibrotic remodeling through the senescence-associated secretory phenotype (SASP). Beyond its fundamental role in intracellular energy metabolism, adenosine triphosphate (ATP) can also be released into the extracellular environment under conditions such as ischemia-reperfusion injury (IRI), mechanical stress, inflammatory stimulation, and cellular damage, where it participates in cellular stress responses through P2X/P2Y purinergic receptors. This article proposes the hypothesis that ATP-induced cellular senescence (AICS) contributes to CVD progression, suggesting that sustained or abnormally enhanced extracellular ATP signaling may promote cardiovascular cell senescence through disruption of Ca²⁺ homeostasis, mitochondrial reactive oxygen species (ROS) accumulation, activation of DNA damage response (DDR) pathways, NLRP3 inflammasome activation, enhanced NF-κB signaling, and persistent maintenance of the SASP. However, ATP signaling is highly dependent on its concentration, exposure duration, receptor subtype, and cellular context, and therefore cannot be simply regarded as a pro-senescence signal. Further studies using CVD-specific models and human pathological samples are required to establish the causal relationship among ATP/P2 receptor activation, cellular senescence burden, and disease progression.

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Cite

BibTeXRIS
BibTeX
@article{liu2026extracellular,
  title = {{Extracellular ATP Signaling as a Proposed Mechanistic Link to Cellular Senescence in Cardiovascular Diseases.}},
  author = {Xuesong Liu and Jingjing Zhang and Jingjing Lu and Zhihao Hu and Huiting Wei and Linzhu Li and Yufei Yang and Jinhai Liu and Zhaoyu Li and Haoling Zhang and Wangzheqi Zhang},
  journal = {Journal of inflammation research},
  year = {2026},
  month = oct,
  doi = {10.2147/jir.s642699},
  url = {https://europepmc.org/article/MED/42974193},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Extracellular ATP Signaling as a Proposed Mechanistic Link to Cellular Senescence in Cardiovascular Diseases.
AU  - Xuesong Liu
AU  - Jingjing Zhang
AU  - Jingjing Lu
AU  - Zhihao Hu
AU  - Huiting Wei
AU  - Linzhu Li
AU  - Yufei Yang
AU  - Jinhai Liu
AU  - Zhaoyu Li
AU  - Haoling Zhang
AU  - Wangzheqi Zhang
PY  - 2026
DA  - 2026/10/29
JO  - Journal of inflammation research
DO  - 10.2147/jir.s642699
UR  - https://europepmc.org/article/MED/42974193
AB  - Cellular senescence represents a critical pathological process involved in the progression of cardiovascular diseases (CVDs). Senescent endothelial cells, cardiomyocytes, vascular smooth muscle cells (VSMCs), and immune cells can promote inflammatory responses, oxidative stress, extracellular matrix (ECM) degradation, and fibrotic remodeling through the senescence-associated secretory phenotype (SASP). Beyond its fundamental role in intracellular energy metabolism, adenosine triphosphate (ATP) can also be released into the extracellular environment under conditions such as ischemia-reperfusion injury (IRI), mechanical stress, inflammatory stimulation, and cellular damage, where it participates in cellular stress responses through P2X/P2Y purinergic receptors. This article proposes the hypothesis that ATP-induced cellular senescence (AICS) contributes to CVD progression, suggesting that sustained or abnormally enhanced extracellular ATP signaling may promote cardiovascular cell senescence through disruption of Ca²⁺ homeostasis, mitochondrial reactive oxygen species (ROS) accumulation, activation of DNA damage response (DDR) pathways, NLRP3 inflammasome activation, enhanced NF-κB signaling, and persistent maintenance of the SASP. However, ATP signaling is highly dependent on its concentration, exposure duration, receptor subtype, and cellular context, and therefore cannot be simply regarded as a pro-senescence signal. Further studies using CVD-specific models and human pathological samples are required to establish the causal relationship among ATP/P2 receptor activation, cellular senescence burden, and disease progression.
SN  - 1178-7031
ER  -