Open Access

ARTICLE

Lovastatin modulation of YAP/TAZ signaling on cardiomyocyte autophagy and mitochondrial damage in myocardial I/R injury

KAITIAN ZHANG^1,#, MINGZHU LI^2,#,*, JIANPING ZHANG³, JINFENG LI², KUNLANG LI², HUANQIAN LU², JINYAN LV²

1 Department of Cardiovascular Surgery, The People’s Hospital of Gaozhou, Gaozhou, 525200, China
2 Department of Pharmacy, The People’s Hospital of Gaozhou, Gaozhou, 525200, China
3 Department of Pharmacology, School of Pharmacy, Jinan University, Guangzhou, 511436, China

* Corresponding Author: MINGZHU LI. Email:
# Represented equally contribution to this work

(This article belongs to the Special Issue: Cell Death and Inflammation in Signaling and Diseases)

BIOCELL 2024, 48(10), 1489-1501. https://doi.org/10.32604/biocell.2024.053930

Received 14 May 2024; Accepted 27 August 2024; Issue published 02 October 2024

Abstract

Objective: Studies have demonstrated that administering statins promptly following myocardial ischemia/reperfusion (MI/R) can confer cardioprotective benefits. This study investigates whether Lovastatin can modulate the Yes-associated protein/Transcriptional co-activator with PDZ-binding motif (YAP/TAZ) signaling pathway to mitigate cardiomyocyte injury caused by hypoxia/reoxygenation (H/R). Methods: The in vitro MI/R model was established by H/R in rat myocardial H9c2 cells, and the cells were pretreated with varying doses of Lovastatin before reoxygenation. The extent of cellular injury was evaluated by measuring the myocardial enzyme content and cell viability. The levels of oxidative stress and inflammatory factors were quantified by enzyme-linked immunosorbent assay (ELISA). Mitochondrial function was evaluated by detecting mitochondrial reactive oxide species (ROS), oxygen consumption rate (OCR), mitochondrial permeability transition pore (MPTP), adenosine 5′-triphosphate (ATP), mitochondrial membrane potential (MMP), and Ca²⁺. Western blotting (WB) and immunofluorescence assays were applied to detect the proteins related to apoptosis, autophagy, and YAP/TAZ signaling. YAP overexpression plasmid (Ov-YAP) was constructed for mechanism verification. Results: H/R leads to a reduction in H9c2 cell viability, and an elevation in the contents of myocardial enzymes, inflammatory factors, and oxidative stress. The apoptosis and autophagy were increased, and yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) expression levels were up-regulated in the H/R group. Nevertheless, all these changes were dose-dependently reversed by Lovastatin. Meanwhile, Lovastatin restored the levels of MMP, ATP, MPTP opening, and Ca²⁺, and reduced OCR in H9c2 cells exposed to H/R. Nevertheless, Ov-YAP markedly attenuated the function of Lovastatin on apoptosis, autophagy, inflammation, and oxidative stress in H9c2 cells exposed to H/R. Conclusion: The result indicated that Lovastatin played a protective role in H/R-induced H9c2 cells by inhibiting YAP/TAZ signaling.

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