Adenosine triphosphate homeostasis in cardiovascular cell-fate transitions: Adenosine triphosphate-induced cellular senescence and adenosine triphosphate-induced cell death

Table 1 Experimental evidence linking ATP regulation to cardiovascular cell-fate transitions

Cell type	Disease model/stress context	ATP compartment measured	Direction of ATP alteration	Representative mechanism	Cell-fate outcome	Evidence of causality	Level of evidence	Ref.
Cardiomyocytes	Myocardial ischemia/reperfusion injury	Extracellular ATP	↑ Extracellular ATP accumulation due to impaired degradation	RBM15-mediated m6A modification increases Entpd1/CD39 expression and enhances extracellular ATP hydrolysis	Reduced myocardial injury and improved cardiac protection	CD39 upregulation decreases extracellular ATP accumulation and alleviates ischemia–reperfusion injury	Animal experimental evidence with molecular intervention	[8]
Cardiomyocytes	Mitochondrial dysfunction and oxidative stress	Intracellular ATP	↓ Intracellular ATP generation	LETM1 dysregulation impairs oxidative phosphorylation and mitochondrial function	Cardiomyocyte stress, apoptosis, and impaired mitochondrial homeostasis	Restoration of mitochondrial function improves cellular survival	Cellular experimental evidence	[9]
Cardiomyocytes	Myocardial injury and ischemic stress	Extracellular ATP	↑ Extracellular ATP release	PANX1-mediated ATP release activates purinergic signaling involving P2X7-related pathways	Cardiomyocyte injury, apoptosis, and inflammatory remodeling	PANX1/P2X7 pathway interference attenuates injury-associated responses	Cellular and animal mechanistic evidence	[18]
Cardiac macrophages and cardiomyocytes	Hepatic ischemia–reperfusion-induced remote cardiac injury	Circulating extracellular ATP	↑ Circulating ATP	Extracellular ATP activates macrophage P2X7 receptor, inducing NLRP3 inflammasome assembly and GSDMD-dependent pyroptosis	Cardiomyocyte pyroptosis and cardiac dysfunction	P2X7 inhibition, macrophage depletion, and pathway interference reduce cardiac injury	Animal model with mechanistic validation	[19]
Cardiomyocytes	Hypoxia/reoxygenation injury	Intracellular ATP-associated mitochondrial metabolism	↓ ATP availability associated with mitochondrial dysfunction	Mitochondrial stress causes ROS accumulation, antioxidant defense impairment, and lipid peroxidation	Ferroptotic cell death	Mitochondrial protective intervention restores metabolic function and reduces ferroptosis markers	Cellular experimental evidence	[20]
Cardiomyocytes	5-Fluorouracil-induced myocardial injury	Intracellular ATP	↓ Mitochondrial ATP production	Mitochondrial injury and impaired autophagic quality control reduce bioenergetic capacity	Cardiomyocyte apoptosis and myocardial fibrosis	Mitochondrial protection reduces myocardial injury phenotype	Animal experimental evidence	[21]
Cardiomyocytes	Cardiac aging and senescence	Intracellular ATP	↓ ATP availability associated with energetic dysfunction	Disruption of ATP synthase organization and impaired Ca²+ handling impair cellular energetics	Senescence-associated phenotype and contractile dysfunction	ATP synthase disruption correlates with senescence-associated dysfunction	Experimental cellular and animal evidence	[22]
Vascular smooth muscle cells	Aging-related vascular calcification	Intracellular ATP and mitochondrial homeostasis	↓ Mitochondrial ATP generation	SIRT1/PGC-1α/Mfn2-associated mitochondrial dysfunction affects energy metabolism	Cellular aging and vascular remodeling	Pathway modulation improves mitochondrial homeostasis	Animal and molecular experimental evidence	[23]
Cardiomyocytes	Myocardial infarction and cardiovascular remodeling	Extracellular ATP signaling	↑ Extracellular ATP-dependent signaling	ATP-P2X7 receptor activation promotes inflammatory signaling and NLRP3-related responses	Pyroptosis, fibrosis, and cardiac dysfunction	P2X7 inhibition or pathway blockade improves cardiac phenotype	Experimental animal and molecular evidence	[24]
Cardiovascular tissues/endothelium	Hypertension, atherosclerosis, and vascular inflammation	Extracellular ATP signaling	↑ Extracellular ATP signaling activity	P2X7 activation promotes inflammatory cytokine production, oxidative stress, and vascular remodeling	Endothelial dysfunction and vascular remodeling	P2X7 inhibition reduces inflammatory cardiovascular injury	Experimental and translational evidence	[25]

ATP: Adenosine triphosphate; ROS: Reactive oxygen species; NLRP3: NOD-like receptor family pyrin domain-containing 3.