# Mild hypothermia (35°C) reduces myocardial ischemia-reperfusion injury and attenuates hypoxia induced apoptosis of H9C2 cardiomyocytes by changing the phosphorylation level of Connexin43 (Cx43) protein

**Authors:** Yuanming Lu, Fang Wang, Nanping Xiao, Zilian Fan, Lan Xiong, Jing Kou, Tianxun Wang, Dianyuan Li

PMC · DOI: 10.4314/ahs.v25i1.18 · African Health Sciences · 2025-03-01

## TL;DR

Mild hypothermia at 35°C helps protect heart cells from damage during reperfusion by altering Cx43 protein activity, reducing cell death and improving heart function.

## Contribution

This study reveals that mild hypothermia reduces myocardial injury by modulating Cx43 phosphorylation and apoptosis pathways.

## Key findings

- Mild hypothermia reduces infarction area and enhances myocardial function in rats.
- In H9C2 cells, mild hypothermia decreases apoptosis and increases anti-apoptotic factors.
- Phosphorylated Cx43 levels are elevated under mild hypothermia, contributing to cell protection.

## Abstract

The purpose of this study was to investigate the effect of connexin 43 (Cx43) on myocardial cell apoptosis under mild hypothermia and its potential for treating ischemia reperfusion injury.

In vivo experiments were conducted on rats, using an ischemia-reperfusion model, small animal ultrasound imaging system, and relevant biochemical assays to measure myocardial function, infarction area, and tissue damage. In vitro experiments were performed on H9C2 cells using an oxygen-glucose deprivation and recovery model, and various assays were used to assess cell viability, apoptosis, and biochemical changes.

Mild hypothermia (35°C) was found to reduce ischemia-reperfusion injury, enhance myocardial function, decrease infarction area, and increase the expression of phosphorylated Cx43 and protein kinase C in myocardial tissue. In vitro, mild hypothermia enhanced cell viability, decreased gap junction permeability, downregulated pro-apoptotic factors, and upregulated anti-apoptotic factors, while also increasing the levels of calcium and superoxide dismutase and decreasing the level of malondialdehyde.

Mild hypothermia can protect against myocardial ischemia-reperfusion injury by regulating the level of phosphorylated Cx43 protein, which reduces myocardial cell apoptosis and enhances cardiac function. This study highlights the potential therapeutic benefits of mild hypothermia in treating ischemia-reperfusion injury.

## Linked entities

- **Proteins:** CONNEXIN 43 (CONNEXIN 43 protein), GJA1 (gap junction protein alpha 1)
- **Chemicals:** malondialdehyde (PubChem CID 10964)
- **Species:** Homo sapiens (taxon 9606), Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Gja1 (gap junction protein, alpha 1) [NCBI Gene 24392] {aka Cx43, Cxnk1}
- **Diseases:** infarction (MESH:D007238), hypoxia (MESH:D000860), ischemia (MESH:D007511), ischemia reperfusion injury (MESH:D015427), myocardial ischemia (MESH:D017202), myocardial (MESH:D009202), hypothermia (MESH:D007035)
- **Chemicals:** calcium (MESH:D002118), glucose (MESH:D005947), oxygen (MESH:D010100), malondialdehyde (MESH:D008315)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

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## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12865057/full.md

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Source: https://tomesphere.com/paper/PMC12865057