MiR-133a mimic alleviates T1DM-induced systolic dysfunction in akita: An MRI-based study

Shyam Sundar Nandi, Hamid Reza Shahshahan, Quanliang Shang, Shelby Kutty, Michael Boska, Paras Kumar Mishra

Research output: Contribution to journalArticle

Abstract

Diabetic cardiomyopathy is a leading cause of heart failure. Developing a novel therapeutic strategy for diabetic cardiomyopathy and characterizing animal models used for diabetes mellitus (DM) are important. Insulin 2 mutant (Ins2+/-) Akita is a spontaneous, genetic, mouse model for T1DM, which is relevant to humans. There are contrasting reports on systolic dysfunction and pathological remodeling (hypertrophy and fibrosis) in Akita heart. Here, we used magnetic resonance imaging (MRI) approach, a gold standard reference for evaluating cardiac function, to measure ejection fraction (indicator of systolic dysfunction) in Akita. Moreover, we performed Wheat Germ Agglutinin (WGA) and hematoxylin and Eosin stainings to determine cardiac hypertrophy, and Masson’s Trichrome and picrosirius red stainings to determine cardiac fibrosis in Akita. MiR-133a, an anti-hypertrophy and anti-fibrosis miRNA, is downregulated in Akita heart. We determined if miR-133a mimic treatment could mitigate systolic dysfunction and remodeling in Akita heart. Our MRI results revealed decreased ejection fraction in Akita as compared to WT and increased ejection fraction in miR-133a mimic-treated Akita. We also found that miR-133a mimic treatment mitigates T1DM-induced cardiac hypertrophy and fibrosis in Akita. We conclude that Akita shows cardiac hypertrophy, fibrosis and systolic dysfunction and miR-133a mimic treatment to Akita could ameliorate them.

Original languageEnglish (US)
Article number1275
JournalFrontiers in Physiology
Volume9
Issue numberOCT
DOIs
StatePublished - Oct 10 2018

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Fibrosis
Magnetic Resonance Imaging
Cardiomegaly
Diabetic Cardiomyopathies
Hypertrophy
Staining and Labeling
Wheat Germ Agglutinins
Genetic Models
Hematoxylin
Eosine Yellowish-(YS)
MicroRNAs
Diabetes Mellitus
Down-Regulation
Animal Models
Heart Failure
Insulin
Therapeutics

Keywords

  • Cardiac dysfunction
  • Fibrosis
  • Hypertrophy
  • Ins2+/- Akita
  • MRI
  • MiR-133a

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

MiR-133a mimic alleviates T1DM-induced systolic dysfunction in akita : An MRI-based study. / Nandi, Shyam Sundar; Shahshahan, Hamid Reza; Shang, Quanliang; Kutty, Shelby; Boska, Michael; Mishra, Paras Kumar.

In: Frontiers in Physiology, Vol. 9, No. OCT, 1275, 10.10.2018.

Research output: Contribution to journalArticle

Nandi, Shyam Sundar ; Shahshahan, Hamid Reza ; Shang, Quanliang ; Kutty, Shelby ; Boska, Michael ; Mishra, Paras Kumar. / MiR-133a mimic alleviates T1DM-induced systolic dysfunction in akita : An MRI-based study. In: Frontiers in Physiology. 2018 ; Vol. 9, No. OCT.
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