Metabolic dysfunction-associated steatotic liver disease and heart failure with preserved ejection fraction: A state-of-the-art review

Table 1 Mechanistic evidence linking disease progression in metabolic dysfunction-associated liver disease and heart failure with preserved ejection fraction

Ref.	Mechanistic link	Model
Nasiri-Ansari et al[212], 2021	Empagliflozin attenuates MASLD progression in ApoE-/- mice by promoting hepatic autophagy, reducing ER stress, and inhibiting hepatocyte apoptosis	ApoE-/- mice
Li et al[214], 2021	Dapagliflozin alleviates hepatic steatosis and protects against liver inflammation and fibrosis by reducing lipid accumulation, oxidative stress, and inflammatory responses	Mouse (DIO/MASLD model)
Wang et al[54], 2021	FGF1ΔHBS prevents diabetic cardiomyopathy by maintaining mitochondrial homeostasis and reducing oxidative stress via AMPK/Nur77 suppression	Diabetic mice
Schiattarella et al[67], 2019	iNOS-driven nitrosative stress leads to coronary microvascular inflammation and rarefaction, driving concentric remodeling and diastolic dysfunction in HFpEF	ZSF1 rat model
Hopf et al[182], 2018	Insulin resistance impairs titin phosphorylation via reduced PKG/PKA signaling, increasing cardiomyocyte stiffness and promoting HFpEF in diabetes	Human cardiomyocytes
Slater et al[183], 2019	Metformin improves diastolic function in an HFpEFlike mouse model by lowering titinbased passive stiffness and enhancing titin compliance via PKG-N2BA isoform shift	HFpEF mouse model
Zhao et al[110], 2019	Digoxin inhibits PKM2 and thereby suppresses HIF-1α and NLRP3 inflammasome activation, attenuating steatohepatitis and associated inflammation	Mouse (MASH model)

MASLD: Metabolic dysfunction-associated steatotic liver disease; HFpEf: Heart failure with preserved ejection fraction; iNOS: Inhaled nitric oxide; MASH: Metabolic-associated steatohepatitis.