Dataset Information

Thymosin β4 Protects against Cardiac Damage and Subsequent Cardiac Fibrosis in Mice with Myocardial Infarction.

ABSTRACT:

Background

Inflammation is a critical factor in the development and progression of myocardial infarction and cardiac fibrosis. Thymosin β4 (Tβ4) alleviates the disease process via protective antioxidant and anti-inflammatory mechanisms. Although Tβ4 has been shown to have a protective effect in myocardial infarction, its impact on cardiac fibrosis has not been well reported. In this study, we evaluated the influence of exogenous Tβ4 on myocardial infarction and cardiac fibrosis and explored the possible underlying mechanism.

Methods

Real-time quantitative reverse-transcription PCR (qRT-PCR), immunohistochemistry (IHC), and Western blot were used to analyze Tβ4 expression in acute myocardial infarction (AMI) cardiac tissues. The effects of intraperitoneal adeno-associated virus-Tβ4 (AAV-Tβ4) on ligation-induced AMI in mice were studied using cardiac function parameters, and RT-PCR, Western blot, HE staining, Masson staining, and IHC were used to assess the degree of myocardial fibrosis. The effects of Tβ4 were confirmed in vitro using mouse cardiac myocytes and myofibroblasts.

Results

Tβ4 was shown to be significantly elevated in mice AMI cardiac tissues. In mice, AAV-Tβ4 induced exogenous expression of Tβ4 significantly reduced oxidative damage, inflammation, cardiac dysfunction, and fibrosis. H₂O₂ inhibited mitophagy and increased inflammation in mouse cardiac myocytes via oxidative stress, and Tβ4 substantially reduced mitophagy inhibition and inflammasome activation in myocytes caused by H₂O₂. Furthermore, Tβ4 decreased cardiac myofibroblast growth and reduced TGF-β1-induced activation.

Conclusions

AAV-Tβ4 induced expression of Tβ4 reduced inflammation, heart damage, and eventual fibrosis in vivo. Tβ4 helped to reduce oxidative stress, promote mitophagy, and alleviate inflammation and fibrosis. Exogenous supplementation of Tβ4 might be a promising therapeutic agent for treating myocardial infarction as well as cardiac fibrosis.

SUBMITTER: Wang F

PROVIDER: S-EPMC9187458 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Thymosin β4 Protects against Cardiac Damage and Subsequent Cardiac Fibrosis in Mice with Myocardial Infarction.

Wang Fei F He Yajuan Y Yao Naijuan N Ruan Litao L Tian Zhen Z

Cardiovascular therapeutics 20220603

<h4>Background</h4>Inflammation is a critical factor in the development and progression of myocardial infarction and cardiac fibrosis. Thymosin β4 (Tβ4) alleviates the disease process via protective antioxidant and anti-inflammatory mechanisms. Although Tβ4 has been shown to have a protective effect in myocardial infarction, its impact on cardiac fibrosis has not been well reported. In this study, we evaluated the influence of exogenous Tβ4 on myocardial infarction an ...[more]

PMID: 35712678

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Project description:PURPOSE:Oestrogen receptor β is believed to exert a cardioprotective effect against ischaemic injury. Nonetheless, the mechanism underlying its protective action remains to be fully elucidated. Recently, increased attention has been focused on Notch1 signalling for ameliorating cardiac ischaemic injury. Here, we hypothesised that oestrogen receptor β activation attenuates myocardial infarction (MI)-induced cardiac damage by modulating the Notch1 signalling pathway. METHODS:Male C57BL/6 mice were used to establish an MI model through the ligation of the anterior descending branch of the left coronary artery. Two chemical drugs, 2,3-Bis(4-hydroxyphenyl)-propionitrile (DPN) and N-[N-(3,5-difluorophenacetyl)-l-alanyl]-s-phenylglycine t-butyl ester (DAPT), a specific inhibitor of Notch1 signalling) were administered via intraperitoneal injection to change oestrogen receptor β and Notch1 activities. Immunohistochemistry, western blot analysis, enzyme-linked immunosorbent assay (Elisa) assessment and echocardiography were used in this study to analyse cardiac oxidative stress, apoptosis, infraction volume, fibrosis and cardiac function. RESULTS:DPN-mediated oestrogen receptor β activation effectively protected cardiomyocytes from MI-induced oxidative damage and apoptosis. Furthermore, oestrogen receptor β activation reduced the infarct size and lowered the levels of myocardial enzymes in the serum, thereby leading to greater overall cardiac function improvement. Ischaemic injury-induced myocardial fibrosis was attenuated by oestrogen receptor β activation. Nevertheless, all of these cardioprotective effects of oestrogen receptor β activation were almost abrogated by DAPT administration, i.e. DAPT attenuated the anti-oxidative and anti-apoptotic effects and the decrease in infarct and fibrotic areas and reversed cardiac functional recovery. The levels of phospho-phosphatidylinositol-3-kinase (PI3K) and phospho-protein kinase B (Akt) were increased after DPN administration, and this change was reversed after DAPT was administered. CONCLUSIONS:All of these new findings indicate that oestrogen receptor β activation is effective in ameliorating MI-induced cardiac dysfunction by enhancing Notch1 signalling and that PI3K/Akt signalling is the downstream mediator.

Dataset Information

Thymosin β4 Protects against Cardiac Damage and Subsequent Cardiac Fibrosis in Mice with Myocardial Infarction.

Background

Methods

Results

Conclusions

Publications

Thymosin <i>β</i>4 Protects against Cardiac Damage and Subsequent Cardiac Fibrosis in Mice with Myocardial Infarction.

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