Original Research ARTICLE
MiR-133a mimic alleviates T1DM-induced systolic dysfunction in Akita: A MRI-based study
- 1Cellular & Integrative Physiology, University of Nebraska Medical Center, United States
- 2Department of Radiology, University of Nebraska Medical Center, United States
- 3Pediatric Cardiology, University of Nebraska Medical Center, United States
Diastolic dysfunction leading to systolic dysfunction is a hallmark of diabetic cardiomyopathy. However, there is a controversy on whether Akita mouse, a model for T1DM (type 1 diabetes mellitus), shows systolic dysfunction. In the present study, we used magnetic resonance imaging (MRI), a gold standard reference for evaluation of cardiac dysfunction, to determine systolic dysfunction in Akita. In Akita heart, miR-133a, a cardioprotective and the most abundant miRNA in the human heart, is downregulated. Here, we investigated if miR-133a mimic treatment could improve systolic dysfunction in Akita by measuring ejection fraction (EF). To evaluate the anti-hypertrophy and anti-fibrosis effects of miR-133a, we measured cardiac hypertrophy and fibrosis in Akita treated with or without miR-133a mimic. Our results showed ~24% decrease in EF in Akita as compared to WT (EF, WT=60.25±3.96, Akita=46.00±5.83; P=0.06) suggesting systolic dysfunction. However, miR-133a mimic treatment improved EF in Akita (EF, Akita=46.00±5.83, Akita+miR-133a=62.4± 1.89; P=0.02) demonstrating the potential of miR-133a mimic to improve systolic function in Akita. Pathological remodeling in Akita heart was evaluated by determining hypertrophy and fibrosis. We found increased cardiac hypertrophy and fibrosis in Akita, which were decreased by miR-133a mimic treatment. Our findings support systolic dysfunction in Akita and suggest a new potential therapeutic candidate, miR-133a mimic, to mitigate systolic dysfunction and alleviated pathological remodeling in T1DM heart.
Keywords: Ins2+/- Akita, miR-133a, cardiac function, MRI, Fibrosis, Hypertrophy
Received: 18 Jan 2018;
Accepted: 21 Aug 2018.
Edited by:Narasaiah Kolliputi, University of South Florida, United States
Reviewed by:Xiao-feng Yang, MD, PhD, Lewis Katz School of Medicine, Temple University, United States
Shyam S. Bansal, The Ohio State University, United States
Copyright: © 2018 Nandi, Shahshahan, Shang, Kutty, Boska and Mishra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Paras Kumar Mishra, University of Nebraska Medical Center, Cellular & Integrative Physiology, 985850 Nebraska Medical Center, Omaha, 68198, NE, United States, email@example.com