PHLDA1 improves ischemic cardiomyopathy by regulating the PI3K/AKT signaling axis
10.3969/j.issn.1673-4130.2025.17.015
- VernacularTitle:PHLDA1通过调控PI3K/AKT信号轴改善缺血性心肌病
- Author:
Tianci HU
1
;
Jinhui WANG
Author Information
1. 厦门市儿童医院(复旦大学附属儿科医院厦门医院)医学检验科,福建 厦门 361006
- Keywords:
ischemic cardiomyopathy;
Pleckstrin homology-like Domain,Family A,Member 1;
phos-phatidylinositol 3-kinase/protein kinase B
- From:
International Journal of Laboratory Medicine
2025;46(17):2131-2136
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the potential role and underlying mechanisms of Pleckstrin homology-like Domain,Family A,Member 1(PHLDA1)in ischemic cardiomyopathy(ICM).Methods In this study,male Balb/C mice were administered control AAV9-U6 and AAV9-U6-shPHLDA1 vectors via tail vein injec-tion.Two weeks later,mice were randomly divided into four groups:two groups underwent coronary artery ligation to induce an acute myocardial infarction(MI)model,while the other two groups underwent sham sur-gery.Protein expression levels were assessed using Western blotting,immunofluorescence,and real-time fluo-rescence quantitative PCR(qPCR).Myocardial morphology and cardiac fibrosis progression were evaluated through immunohistochemistry and Masson staining.Results The results of immunoblotting and immunoflu-orescence experiments showed that PHLDA1 expression was elevated in the myocardial tissue of the construc-ted MI mouse model.Inhibiting the expression of PHLDA1 in the MI mouse model could significantly improve its survival rate.Immunohistochemical and Masson staining results showed that the cardiac outcome of MI mice was negatively correlated with PHLDA1 expression(P<0.05).In the MI model,inhibiting the expres-sion of PHLDA1 could promote the phosphorylation of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)in myocardial tissue.Overexpression of PHLDA1 significantly inhibited the phosphorylation of PI3K/Akt in myocardial tissue.Conclusion PHLDA1 plays an important role in improving the cardiac outcomes of ICM,and inhibiting PHLDA1 expression can alleviate ischemic cardiomyopathy by promoting PI3K/Akt phos-phorylation.