Adenosine triphosphate-induced cell death in heart failure: Is there a link?

Table 1 Experimental studies examining the role of adenosine triphosphate-induced cell death in cardiomyopathy

Ref.	Year	Model	Marker(s)	Compound/target	Effect(s)
Wu et al[41]	2024	LPS-induced SIC model	LVEF, LVFS, SV, BNP and IL-1β and IL-18	IP3R2	The up-regulation of NLRP3 Leads to GSDMD-induced myocardial tissue pyroptosis
Croteau et al[40]	2023	The high fat-sucrose diet-induced diabetic cardiomyopathy mice model	PCr/ATP	Ertugliflozin	Decreases elevated intracellular sodium
Belosludtseva et al[39]	2023	ISO-induced myocardial injuries	TnI, the ratio of AST/ALT, level of LV myocardial ATP	Uridine	Inhibit ISO-induced excessive production of ROS and lipid peroxidation in rat heart mitochondria
Zhang et al[38]	2016	Cardiotoxicity of ADR	PGC-1α, NRF-1 and TFAM	Cryptotanshinone	Increase the activity of complexes other than Complex II, significantly promoting the production of ATP energy
Ding et al[37]	2023	Doxorubicin-induced cardiomyopathy	Enzymes CK, CK-MB and LDH	SGI	Increase ATP levels and mitochondrial membrane potential and inhibit intracellular ROS
Panxia et al[36]	2019	Doxorubicin-induced cardiomyopathy	SESN2	SESN2	Improve mitochondrial function and mitochondrial autophagy to prevent Dox-induced cardiotoxicity
Song et al[35]	2021	DCM	caspase 1	SIRT3	Promote myocardial necrotic apoptosis in DCM mice
Wang et al[34]	2025	CLP-SIC mice model	SOD and GSH-Px	PGJXD	Inhibit inflammatory responses and improve cardiomyocyte apoptosis, alleviate mitochondrial structural abnormalities in CLP model, reduce oxidative stress damage and promote energy synthesis
Guo et al[32]	2025	STZ/HFD-induced mouse model	TNF-α, IL-6, Masson Trichrome staining, ORO staining	SIRT2	SIRT2-mediated deacetylation at K239 enhances CPT2 ubiquitination
Yuan et al[33]	2025	CLP mouse model	LDH	5'tiRNA-33-CysACA-1	The key molecule PGC-1α promotes the development of SCM by targeting mitochondrial biogenesis

LPS: Lipopolysaccharide; SIC: Silicon carbide; LVEF: Left ventricular ejection fraction; BNP: B-Type Natriuretic Peptide; SV: Stroke volume; IP3R2: Inositol 1,4,5-triphosphate receptor, type 2; LVFS: Left ventricular fractional shortening; IL-1β: Interleukin-1 beta; IL-18: Interleukin-18; GSDMD: Gasdermin; ATP: Adenosine triphosphate; PCr: Creatine phosphate; ISO: Isoproterenol; TnI: Troponin I; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ROS: Reactive oxygen species; ADR: Adverse drug reaction; PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1 alpha; NRF-1: Nuclear respiratory factor 1; TFAM: Mitochondrial transcription factor A; CK: Creatine kinase; CK-MB: Creatine kinase MB; LDH: Lactate dehydrogenase; DCM: Diabetic cardiomyopathy; SESN2: Sestrin2; SIRT3: Sirtuin 3; CLP: The cecal ligation and puncture; SOD: Superoxide dismutase; GSH-Px: Glutathione peroxidase; PGJXD: Po-Ge-Jiu-Xin decoction; SIRT2: Sirtuin 2; STZ/HFD: High-fat diet and streptozotocin; TNF-α: Tumour necrosis factor alpha; IL-6: Interleukin-6; ORO: Oil Red O; SCM: Septic cardiomyopathy.

Table 2 Experimental studies examining the role of adenosine triphosphate-induced cell death in ischemia-reperfusion injury

Ref.	Year	Model	Marker(s)	Compound/target	Effect(s)
Zhang et al[70]	2024	Temporary ligation of the LAD for 40 minutes to induce myocardial I/R injury	cTnT, LVEF, LVFS, LVEDD and LVESD	B. infantis or its metabolite inosine	Activate A2AR
Chen et al[69]	2024	A thoracotomy was performed, and reversible sutures were placed around the LAD. By tightening the sutures for 30 minutes and then loosening them, myocardial I/R was induced	NIR imaging	IR-780	Binds to the F0F1-ATP synthase of cardiomyocytes, inducing mitochondria to enter a "resting state"
Chen et al[68]	2022	Mice undergo 60 minutes of ischemia in the LAD by ligating the artery, followed by 120 minutes of reperfusion after releasing the ligation to establish an IRI model	IL-6, IL-10, TNF-α, MIF, P-AMPK α, GLUT4 and Bcl-2	Dexmedetomidine	α2-AR stimulant
Rusiecka et al[67]	2023	Perform a left thoracotomy to access the heart, suture around the LAD with 8-0 Prolene suture, and form a loop using a small piece of polyethylene tubing. Induce ischemia by pulling the loop and maintain the occlusion for 30 minutes. Reperfuse after releasing the clamp for 24 hours	cTnI	Panx1	Increased mitochondrial ATP content
Flori et al[66]	2023	Acute myocardial injury and I/R injury caused by coronary artery occlusion	cTnI	ERU, mitoKATP channel	Activate mitoK channels, mitoKv7.4, and mitoKATP channels
Wu et al[65]	2022	Ligate the LAD to construct an in vivo I/R model	Infarct size, LDH levels, and serum cTnT levels	IF1	Block the reversal of F1Fo-ATP synthase; Activate AMPK
Wang et al[64]	2023	Exposure of the heart is achieved through a left thoracotomy, and AMI is induced by ligating the LAD at its temporal aspect for 30 minutes, followed by releasing the ligation to cause reperfusion injury after 30 minutes	LDH and CK-MB	AASP	Increase mitochondrial membrane potential, restore ATP synthase activity
Huang et al[63]	2024	Induce myocardial ischemia through methods such as coronary artery ligation, and then restore blood flow after a certain period to simulate the reperfusion process	LDH, CK, Acetylation level of SF3A2	Ginsenoside Rb2	Inhibit p300-mediated acetylation at lysine 10 of SF3A2 to promote selective splicing of the Fscn1 gene, thereby enhancing Fscn1 expression
Cai et al[62]	2023	LAD ligation mouse model	LDH, ACSL4, TfR, SLC7A11, GPX4 and 4- HNE	Alox15/15-HpETE	Promote the binding of Pgc1α with ubiquitin ligase ring finger protein 34
Chen et al[71]	2024	An open-chest surgery was performed to expose the heart, and then the LAD was sutured with 9-0 suture thread	cTnI and CK-MB	GAS	GAS improved mitochondrial autophagy by PINK1/Parkin

LAD: Left anterior descending coronary artery; cTnT: Cardiac troponins T; cTnI: Cardiac troponins I; LVEF: Left ventricular ejection fraction; LVFS: Left ventricular fractional shortening; LVEDD: Left ventricular end-diastolic diameter; LVESd: Left ventricular end-systolic diameter; B. infantis: Bifidobacterium infantis; A2AR: Adenosine A2A receptors; NIR: Near-infrared; IRI: Ischemia/reperfusion injury; IL-6: Interleukin-6; IL-10: Interleukin-10; TNF-α: Tumour necrosis factor alpha; MIF: Macrophage migration inhibitory factor; P-AMPK α: Phosphorylated AMP-activated protein kinase α; GLUT4: Glucose transporters type 4; Bcl-2: B cell lymphoma 2; α2-AR: Α2-adrenergic receptor; ERU: Erucin; mitoKATP: Mitochondrial ATP-sensitive potassium channel; IF1: F1Fo-ATPase inhibitor 1; AMI: Acute myocardial ischemia; TfR: Transferrin receptor; SLC7A11: Solute carrier family 7a member 11; GPX4: Glutathione peroxidase 4; 4-HNE: 4-hydroxy-2-nonenal; Pgc1α: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; GAS: Gastrodin; PINK1: PTEN-induced kinase 1.

Table 3 Experimental studies examining the roles of adenosine triphosphate-induced cell death in heart failure with preserved ejection fraction and heart failure

Ref.	Year	Model	Marker(s)	Compound/target	Effect(s)
Schiattarella et al[98]	2021	The model combines metabolic alterations (exposure to HFD) and endothelial dysfunction-driven hypertension (modeled using a NOS inhibitor, L-NAME) to simulate clinical HFpEF	FoxO1, STUB1	Xbp1s-FoxO1	Activate E3 ubiquitin ligase STUB1
Yan et al[97]	2024	TAC-induced chronic HF and doxorubicin-induced acute HF mouse models	Mitochondrial OCR Analysis, LDH Activity and CK-MB	DDX17	Promoting mitochondrial homeostasis through the BCL6-DRP1 pathway
Zhang et al[96]	2023	Injection of DOCA, Ang II, and WD for 18 weeks to establish HFpEF pigs	Th, IL-6 and TNF-α	Dapagliflozin	Elevate β-hydroxybutyrate-activated citrate synthase activity
Zhang et al[95]	2024	Continuous infusion of AngII induces cardiac remodeling	LAMP1, LC3II, p62, IL-6, MCP-1, IL-1β	Schaftoside	Inhibit CaMKII-δ activity
Shou et al[94]	2022	Establishing a hypertension-induced HFpEF model in Dahl/SS rats with high-salt feeding	Mfn2 and Drp1	PINK1	Phosphorylation of Drp1S616 to improve mitochondrial fission and alleviate mitochondrial dysfunction
He et al[93]	2022	High-salt diet induces HFpEF	LVEF and E/A ratio, Masson's trichrome staining, WGA staining	Canagliflozin	Upregulate p-AMPK and SIRT1, and significantly induce the expression of PGC-1α
Shao et al[92]	2024	Ligation of the LAD induced	RXRa, Ndufs4	AS-III	Activate RXRa dimer
Zhang et al[91]	2024	DOX-induced HF	IL-1β, IL-18, TNF-α, TLR2	Circ-0006332	Downregulate miR-143 and upregulate TLR2 to stimulate cardiomyocyte pyroptosis
Lyu et al[90]	2023	Ligation of LAD induces HF	ATP, AMP, ADP	Empagliflozin	Downregulate the expression of mitochondrial fission proteins and upregulate the expression of mitochondrial fusion proteins in HF mice
Yang et al[89]	2022	DOX-induced HF	BNP, ATP1α1	Trimetazidine	Inhibit KAT

HFD: High-fat diet; FoxO1: Forkhead box O 1; STUB1: STIP1 homology and U-box-containing protein 1; NOS: Nitric oxide synthase; L-NAME: Nω-nitro-L-arginine methyl ester; TAC: Transverse aortic constriction; OCR: Oxygen consumption rate; DDX17: DDEAD-box helicase 17; CaMKII-δ: Ca²⁺/calmodulin-dependent kinase II-δ; BCL6-DRP1: B-cell lymphoma 6 - dynamin-related protein 1; DOCA: Deoxycorticosterone acetate; WD: Western diet; Th: Tyrosine Hydroxylase; LAMP1: Lysosome associated membrane proteins 1; LC3II: Light chain 3 II; MCP-1: Monocyte chemoattractant protein-1; Mfn2: Mitofusin 2 protein; Drp1: Dynamin-related protein 1; PINK1: PTEN-induced kinase 1; WGA: Wheat germ agglutinin; RXRa: Retinoid X receptor protein a; Ndufs4: Ubiquinone oxidoreductase subunit S4; AS-III: Arsenic-III ;DOX: Doxorubicin; TLR2: Toll-like receptor-2; Circ-0006332; ATP1α1: Na²⁺/ K⁺ATPase subunit alpha 1; KAT: 3-ketoacyl-CoA thiolase.