Vol 26, No 4 (2019)
Original articles — Basic science and experimental cardiology
Published online: 2018-04-25

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

Xuhui Ma1, Pengfei Hu2, Haifeng Chen3, Tianfu Fang1
Pubmed: 29718531
Cardiol J 2019;26(4):394-404.


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 forma­tion 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 assess­ments 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 apop­tosis, 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-pro­tective role in ischemic heart disease via inactivation of the PDK1/Pten/Akt pathway.

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