Loss of AMIGO2 causes dramatic damage to cardiac preservation after ischemic injury.

Abstract

BACKGROUND:

Recent studies have identified amphoterin-induced gene and open reading frame (AMIGO2). The role of AMIGO2 in tumour research is well-studied, but its role in ischemic heart diseases is seldom reported. In the present study, the role of AMIGO2 in myocardial infarction (MI) is under investigation for the first time.

METHODS:

For in vitro studies, cardiomyocytes (CMs) and endothelial cells (ECs) were isolated from both AMIGO2 knockout (KO) and WT mice. The apoptosis of CMs was tested after 48 h of ischemic stimulation. A proliferation test was implemented after 7 days of normoxic incubation and tube forma-tion on ECs. For in vivo studies, the MI model was built in mice hearts. Echocardiographic evaluation was performed at 3 days and 28 days post-MI, while the hemodynamics test was performed at 28 days post-MI. The histological results of the apoptosis, proliferation, angiogenesis and infarct zone assess-ments were determined using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) assay, Ki67 staining, a-SMA/CD31 immunostain and the Masson-Trichrome method, respectively. The expression changes of the Akt pathway and related proteins were confirmed using both quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot.

RESULTS:

The present results demonstrated that AMIGO2 deficiency caused more CMs suffering apop-tosis, lower proliferation and less angiogenesis in vitro and in vivo. Weaker cardiac function and larger scar formation were detected in AMIGO2 KO mice, and increased expression of active-caspase-3 and decreased expression of PDK1, p-Akt, Bcl-2/Bax and VEGF occurred.

CONCLUSIONS:

Herein the findings indicate that AMIGO2 deficiency plays an attenuated cardio-pro-tective role in ischemic heart disease via inactivation of the PDK1/Pten/Akt pathway.

• Authors: Xuhui Ma, Pengfei Hu, Haifeng Chen, Tianfu Fang
• Journal: Cardiology journal (Cardiol J) Vol. 26 Issue 4 Pg. 394-404 ( 2019) ISSN: 1898-018X [Electronic] Poland
• PMID: 29718531 (Publication Type: Journal Article)

Chemical References

• Amigo2 protein, mouse
• Apoptosis Regulatory Proteins
• Membrane Proteins
• Nerve Tissue Proteins
• Pdk1 protein, mouse
• Pyruvate Dehydrogenase Acetyl-Transferring Kinase
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Proto-Oncogene Proteins c-akt
• PTEN Phosphohydrolase
• Pten protein, mouse

Topics

• Animals
• Apoptosis
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Cell Hypoxia
• Cell Proliferation
• Cells, Cultured
• Disease Models, Animal
• Endothelial Cells (metabolism, pathology)
• Membrane Proteins (deficiency, genetics)
• Mice, Inbred C57BL
• Mice, Knockout
• Myocardial Infarction (genetics, metabolism, pathology, physiopathology)
• Myocytes, Cardiac (metabolism, pathology)
• Neovascularization, Physiologic
• Nerve Tissue Proteins (deficiency, genetics)
• PTEN Phosphohydrolase (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Pyruvate Dehydrogenase Acetyl-Transferring Kinase (genetics, metabolism)
• Signal Transduction
• Vascular Endothelial Growth Factor A (genetics, metabolism)
• Ventricular Function, Left