Effects of Stem Cells on Myocardial Infarction Repair and Cardiac Electrophysiology Based on Exosomal STAT3 Protein Transport

Xiaoxia SHEN; Chunhui FENG; Xiaodong ZHAO

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Xiaoxia SHEN, Chunhui FENG, Xiaodong ZHAO. Effects of Stem Cells on Myocardial Infarction Repair and Cardiac Electrophysiology Based on Exosomal STAT3 Protein Transport[J]. Journal of Kunming Medical University.

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Effects of Stem Cells on Myocardial Infarction Repair and Cardiac Electrophysiology Based on Exosomal STAT3 Protein Transport

1.
Department of Cardiology，First Hospital of Zhangjiakou，Hebei Zhangjiakou 075000
2.
Department of Cardiology，Second Hospital of Qinhuangdao，Hebei Qinhuangdao 066600，China

Received Date: 2025-09-17

Abstract

Abstract

Objective To investigate the role of bone marrow-derived mesenchymal stem cell （BMSCs）-derived exosomes （Exo） in transferring signal transduction and transcriptional activator 3 （STAT3） protein in myocardial infarction （MI）. Methods A rat MI model was established by ligation of the left anterior descending coronary artery. The animals were randomly divided into Sham, MI, and BMSCs-Exo groups. Additionally, Exo-pcDNA, Exo-pcDNA-STAT3, Exo-si-NC, and Exo-si-STAT3 groups were established to investigate the effects of upregulating or inhibiting STAT3 expression in Exo on cardiac function. At 2 and 4 weeks after surgery, rat electrocardiograms （ECG） and hemodynamic parameters were measured, including left ventricular systolic pressure （LVSP）, left ventricular end-diastolic pressure （LVEDP）, maximum rate of pressure rise in left ventricle （+dp/dtmax）, and maximum rate of pressure decline in left ventricle （−dp/dtmax）. Western blot （WB） analysis was used to detect the expression levels of related proteins in myocardial tissue, including phosphorylated signal transducer and activator of transcription 3 （p-STAT3）, B-cell lymphoma-2 （Bcl-2）, Bcl-2-associated X protein （Bax）, and cleaved caspase-3 （Cleaved-caspase-3）. Results Compared with the MI group, the BMSCs-Exo group showed significant recovery of ST segment, QRS wave, and QT interval （F = 23.462, P < 0.001）, and decreased arrhythmia incidence （χ² = 7.248, P = 0.009）. Simultaneously, LVEDP decreased, and LVSP and ±dp/dtmax improved （F = 19.601, P < 0.001）. In the transfection groups, compared with the Exo-pcDNA group, the Exo-pcDNA-STAT3 group showed elevated S wave amplitude （P < 0.05） and reduced arrhythmia incidence to 37.5%. Compared with the Exo-si-NC group, the Exo-si-STAT3 group showed prolonged QT interval, widened T wave, and decreased S wave amplitude （F = 30.592, P < 0.001）, with arrhythmia rate increased to 87.5%. Cardiac function assessment showed that the Exo-pcDNA-STAT3 group had decreased LVEDP （F = 14.937, P < 0.001）, while the Exo-si-STAT3 group showed elevated ASBP, LVSP, and +dp/dtmax （F = 16.213, P < 0.001）, suggesting increased cardiac workload. WB results showed that the Exo-pcDNA-STAT3 group had upregulated p-STAT3 and Bcl-2 expression, while Bax and Cleaved-caspase-3 were downregulated （F = 331.518, 901.008, 545.635, and 516.670, P < 0.001）; conversely, the Exo-si-STAT3 group showed opposite trends. Conclusion BMSCs-Exo can improve cardiac function in MI rats, reduce myocardial cell apoptosis, and decrease arrhythmia incidence through STAT3 transfer. Upregulation of STAT3 significantly enhances the cardioprotective effects of Exo, whereas downregulation attenuates these effects. This suggests that the BMSCs-Exo-STAT3 axis may be a novel extracellular vesicle therapy target for treating myocardial infarction.
- Bone marrow mesenchymal stem cells,
- Exosomes,
- Signal transducer and activator of transcription 3,
- Myocardial infarction,
- Electrophysiology

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References(18)

References

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