Upregulation of microRNA-532 enhances cardiomyocyte apoptosis in the diabetic heart

Upregulation of microRNA-532 enhances cardiomyocyte apoptosis in the diabetic heart.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1007/s10495-020-01609-1
Journal or Publication Title: Apoptosis
Volume: 25
Number: 5-6
Page Range: pp. 388-399
Date: 2020
Divisions: Diseases of the Aorta Lab
Depositing User: General Admin
Identification Number: 10.1007/s10495-020-01609-1
ISSN: 1360-8185
Date Deposited: 04 Jan 2021 03:42

Type 2 diabetes has a strong association with the development of cardiovascular disease, which is grouped as diabetic heart disease (DHD). DHD is associated with the progressive loss of cardiovascular cells through the alteration of molecular signalling pathways associated with cell death. In this study, we sought to determine whether diabetes induces dysregulation of miR-532 and if this is associated with accentuated apoptosis. RT-PCR analysis showed a significant increase in miR-532 expression in the right atrial appendage tissue of type 2 diabetic patients undergoing coronary artery bypass graft surgery. This was associated with marked downregulation of its anti-apoptotic target protein apoptosis repressor with caspase recruitment domain (ARC) and increased TUNEL positive cardiomyocytes. Further analysis showed a positive correlation between apoptosis and miR-532 levels. Time-course experiments in a mouse model of type 2 diabetes showed that diabetes-induced activation of miR-532 occurs in the later stage of the disease. Importantly, the upregulation of miR-532 preceded the activation of pro-apoptotic caspase-3/7 activity. Finally, inhibition of miR-532 activity in high glucose cultured human cardiomyocytes prevented the downregulation of ARC and attenuated apoptotic cell death. Diabetes induced activation of miR-532 plays a critical role in accelerating cardiomyocytes apoptosis. Therefore, miR-532 may serve as a promising therapeutic agent to overcome the diabetes-induced loss of cardiomyocytes.

Chandrasekera, Dhananjie N. K.
Neale, Joshua P. H.
van Hout, Isabelle
Rawal, Shruti
Coffey, Sean
Jones, Gregory T.
Bunton, Richard
Sugunesegran, Ramanen
Parry, Dominic
Davis, Philip
Manning, Patrick
Williams, Michael J. A.
Katare, Rajesh
Last Modified: 04 Jan 2021 03:42
URI: https://eprints.centenary.org.au/id/eprint/732

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