时间标签：数据日期 2026-11-05 · 生成时间 2026-11-05 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 ｜ 情报发生日期 2026-11-05
研究问题
Current evidence more strongly supports the role of the ATP/P2 receptor axis in amplifying inflammation and vascular stress, while whether it is sufficient to independently induce stable cellular senescence remains to be determined through comprehensive assessment using established senescence markers.Oxidative Stress and DNA Damage-Driven Cellular SenescenceFollowing P2 receptor activation, disruption of Ca2⁺ homeostasis and alterations in mitochondrial metabolism represent critical steps in the progression of ATP-associated cellular stress responses.；Whether ATP signaling itself initiates or maintains a stable senescent phenotype within atherosclerotic plaques remains unresolved.HypertensionThe role of ATP signaling in hypertension is context-dependent.；In hypertension, the key question could be whether this mechanotransduction–purinergic vasodilatory pathway is impaired by chronic pressure overload and endothelial injury in a way that attenuates NO-dependent vasodilatory reserve.Unlike the endothelial vasodilatory pathway, persistently high extracellular ATP in hypertension has been clearly linked with immune inflammatory amplification.
方法
Accordingly, the core ATP signal considered in the AICS hypothesis refers specifically to extracellular ATP acting through P2 purinergic receptors, whereas intracellular ATP depletion or impaired mitochondrial ATP production is treated here as a distinct manifestation of cellular energetic stress.；Using mice deficient in the P2Y2 receptor specifically in endothelial cells (inducible endothelium-specific P2Y2-deficient mice), Wang et al demonstrated that the loss of P2Y2 impaired flow-mediated vasodilation, reduced eNOS activation and elevated arterial blood pressure.8 These findings suggest that endothelial P2Y2 signaling is physiologically required for flow-dependent eNOS/NO activation and vascular tone regulation in normal states, but does not provide direct evidence of cellular senescence.；Extracellular ATP levels are elevated in hypertensive mice and patients, where ATP activates P2X7R signaling resulting in IL-1β production and T cell activation and the development of memory T cells.
核心结论
Following IRI, cellular senescence and SASP activation are also associated with enhanced inflammatory responses, impaired cardiac function, and adverse tissue remodeling.5,6 These findings have established cellular senescence as a critical pathological dimension underlying vascular inflammation, plaque instability, myocardial fibrosis, and ventricular remodeling.Extracellular ATP provides an important conceptual link between cardiovascular injury signals and the activation of cellular senescence programs.；Upon activation, P2X7R promotes Na⁺ and Ca2⁺ influx as well as K⁺ efflux, with K⁺ depletion serving as a critical trigger for NLRP3 inflammasome assembly, caspase-1 activation, and maturation and release of IL-1β.12,32,33 These findings indicate that the ATP/P2X7R axis has a strong capacity to amplify inflammatory responses; however, current evidence does not establish that P2X7R activation alone is sufficient to induce cellular senescence.；More direct evidence from cardiovascular studies demonstrates that genetic P2X7R deficiency (P2X7R knockout) alleviates cardiac aging-associated phenotypes by enhancing mitophagy and improving mitochondrial quality control in cardiomyocytes.10 These findings support a regulatory role for P2X7R in cardiac aging-associated senescence and mitochondrial quality control, but do not establish sustained extracellular ATP elevation as the upstream trigger of these changes.Beyond P2X7R, P2Y receptors can also translate extracellular nucleotide signals into stress responses in vascular wall cells.
局限
However, the effects of ATP signaling are likely to vary depending on cell type, disease stage, and pathological context, and the causal relationship between ATP/P2 receptor activation, senescence burden, and CVD progression requires further validation.This article focuses on the potential pathological role of sustained extracellular ATP signaling within the cardiovascular injury microenvironment.；Its effects depend on ATP concentration and exposure duration, receptor subtype, cell type, and disease stage, and should be interpreted together with evidence of DNA damage, stable cell-cycle arrest in proliferative cell populations, SASP activation, and functional impairment.；Upon activation, P2X7R promotes Na⁺ and Ca2⁺ influx as well as K⁺ efflux, with K⁺ depletion serving as a critical trigger for NLRP3 inflammasome assembly, caspase-1 activation, and maturation and release of IL-1β.12,32,33 These findings indicate that the ATP/P2X7R axis has a strong capacity to amplify inflammatory responses; however, current evidence does not establish that P2X7R activation alone is sufficient to induce cellular senescence.
对本项目的价值
中高价值：属「衰老细胞清除 / SASP 轴」方向；细胞衰老 / senolytics / SASP栏目可用作本项目文献库与综述素材。 ｜ 价值分 3.1/5（★★★☆☆）
全文来源
PubMed PMC JATS（正文 152,097 字符，题名指纹 1.0，已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验）
原文题录
- 中文题名：细胞外 ATP 信号作为心血管疾病细胞衰老的候选机制纽带
- 英文标题：Extracellular ATP Signaling as a Proposed Mechanistic Link to Cellular Senescence in Cardiovascular Diseases.
- 期刊与标识：Journal of inflammation research · PMID 42974193 · DOI 10.2147/JIR.S642699 · PMC PMC13726713