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Cardioprotective mechanism of ω-3 fatty acid icosapent ethyl (IPE) in cardiomyocytes: role in high glucose and shear stress-induced mechano-transduction dysregulation

Pesapane A, Scisciola L, Basilicata MG, Fontanella RA, Balzano N, Capuano A, Zia A, Arshad M et al.

Cardiovascular diabetology, 2025

1 citation

Abstract

Background: Omega-3 fatty acids (FAs) are long-chain fatty acids that have shown cardioprotective effects through lipid lowering, anti-inflammatory, and membrane-stabilizing properties. In this study we investigated the molecular mechanism underlying the cardioprotective effects of icosapent ethyl (IPE), an ethyl ester of omega-3 fatty (EPA), focusing on its role on mechano-transduction, a process linking cardiac contractility to intracellular signaling, that becomes dysregulated in hyperglycaemia or disturbed blood flow, both major contributors to cardiovascular diseases.

Methods: We conducted in vivo meta-analyses to assess the beneficial effects of omega-3 fatty acids on cardiac contractility and inflammation in patients with cardiovascular and cardiometabolic diseases. We investigated the effects of IPE on mechano-transduction, assessing the activation of the YAP/TAZ signalling pathway, in cardiomyocyte cells AC16 exposed to normal (NG) or high glucose (HG) conditions. We defined the role of IPE against hyperglycaemia-induced inflammation, oxidative stress, metabolism, and apoptosis by evaluating key biomarkers by Western Blot and Real-time PCR. We evaluated IPE's impact on YAP/TAZ activation and on gene expression and protein levels of primary markers related to oxidative stress, inflammation, and metabolism in a dynamic flow model of AC16 cardiomyocytes, to mimic in vivo shear stress.

Results: In vivo meta-analyses showed a significant increase of left ventricular…

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