# Mechanism of RNA Oxidation and Its Inhibitor Involved in Ang II‐Induced Cardiomyocyte Hypertrophy

## TL;DR

This study shows that RNA oxidation contributes to heart cell enlargement and that inhibiting this process may help prevent heart failure.

## Contribution

The study identifies a novel mechanism linking RNA oxidation to cardiomyocyte hypertrophy via the ERK–MAPK pathway.

## Key findings

- RNA oxidation, marked by 8-oxoG accumulation, is linked to cardiomyocyte hypertrophy.
- MTH1 overexpression reduces RNA oxidation and ERK–MAPK activation, decreasing cell hypertrophy.
- RNA oxidation may drive age-related heart diseases through ERK–MAPK pathway activation.

## Abstract

To explore the mechanism of RNA oxidation and its inhibitor MTHI involved in cardiomyocyte hypertrophy.

The hypertrophic H9c2 cardiomyocytes were stimulated with different concentrations and times of Ang II (Ang II) to construct a model of hypertensive heart failure in vitro. Transfection of H9c2 cells with the MTH1 overexpression plasmid was performed. The mRNA expression of ANP, BNP, and β‐MHC in each experimental group was detected by PCR. The expression of 8‐oxoG in H9c2 cells was determined by immunofluorescence and enzyme‐linked immunosorbent assay (ELISA). The activation of the ERK–MAPK pathway and the amount of MTH1 protein were detected by WB semi‐quantitative method.

Notably, RNA oxidation is a critical event in cellular senescence, and its accumulation is strongly linked to the aging process and the development of age‐related diseases. In our model of cardiomyocyte hypertrophy, the oxidative damage of RNA was aggravated, and the expression of MTH1 was increased. At the same time, the sequence of ERK–MAPK pathway proteins was activated. It can be seen that the oxidative damage of RNA is related to the process of cardiomyocyte hypertrophy. After transfection of the MTH1 overexpression plasmid into the cardiomyocyte hypertrophy model, we found that the amount of 8‐oxoG decreased, and the activation of ERK–MAPK signaling pathway proteins decreased, and H9c2 cell hypertrophy decreased. Therefore, we concluded that 8‐oxoG may aggravate the hypertrophy of the cardiomyocyte hypertrophy model by activating the ERK–MAPK pathway.

The oxidative damage of RNA is involved in the process of cardiomyocyte hypertrophy. The mechanism may be that 8‐oxoG, a product of RNA oxidation, activates the downstream ERK–MAPK signaling pathway. These findings provide new perspectives for further exploration into the role of RNA oxidation in the pathogenesis of age‐related diseases, particularly heart failure.

The oxidative damage of RNA is involved in the process of cardiomyocyte hypertrophy. The mechanism may be that 8‐oxoG, a product of RNA oxidation, activates the downstream ERK‐MAPK signaling pathway.