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Regulation of Cardiac Expression of the Diabetic Marker MicroRNA miR-29

Overview of attention for article published in PLOS ONE, July 2014
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Title
Regulation of Cardiac Expression of the Diabetic Marker MicroRNA miR-29
Published in
PLOS ONE, July 2014
DOI 10.1371/journal.pone.0103284
Pubmed ID
Authors

Nicholas Arnold, Purushotham Reddy Koppula, Rukhsana Gul, Christian Luck, Lakshmi Pulakat

Abstract

Diabetes mellitus (DM) is an independent risk factor for heart disease and its underlying mechanisms are unclear. Increased expression of diabetic marker miR-29 family miRNAs (miR-29a, b and c) that suppress the pro-survival protein Myeloid Cell Leukemia 1(MCL-1) is reported in pancreatic β-cells in Type 1 DM. Whether an up-regulation of miR-29 family miRNAs and suppression of MCL-1 (dysregulation of miR-29-MCL-1 axis) occurs in diabetic heart is not known. This study tested the hypothesis that insulin regulates cardiac miR-29-MCL-1 axis and its dysregulation correlates with DM progression. In vitro studies with mouse cardiomyocyte HL-1 cells showed that insulin suppressed the expression of miR-29a, b and c and increased MCL-1 mRNA. Conversely, Rapamycin (Rap), a drug implicated in the new onset DM, increased the expression of miR-29a, b and c and suppressed MCL-1 and this effect was reversed by transfection with miR-29 inhibitors. Rap inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling in HL-1 cells. Moreover, inhibition of either mTORC1 substrate S6K1 by PF-4708671, or eIF4E-induced translation by 4E1RCat suppressed MCL-1. We used Zucker diabetic fatty (ZDF) rat, a rodent model for DM, to test whether dysregulation of cardiac miR-29-MCL-1 axis correlates with DM progression. 11-week old ZDF rats exhibited significantly increased body weight, plasma glucose, insulin, cholesterol, triglycerides, body fat, heart weight, and decreased lean muscle mass compared to age-matched lean rats. Rap treatment (1.2 mg/kg/day, from 9-weeks to 15-weeks) significantly reduced plasma insulin, body weight and heart weight, and severely dysregulated cardiac miR-29-MCL1 axis in ZDF rats. Importantly, dysregulation of cardiac miR-29-MCL-1 axis in ZDF rat heart correlated with cardiac structural damage (disorganization or loss of myofibril bundles). We conclude that insulin and mTORC1 regulate cardiac miR-29-MCL-1 axis and its dysregulation caused by reduced insulin and mTORC1 inhibition increases the vulnerability of a diabetic heart to structural damage.

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Mendeley readers

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The data shown below were compiled from readership statistics for 67 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Turkey 1 1%
Unknown 66 99%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 15 22%
Student > Master 11 16%
Researcher 9 13%
Student > Ph. D. Student 6 9%
Student > Doctoral Student 4 6%
Other 9 13%
Unknown 13 19%
Readers by discipline Count As %
Agricultural and Biological Sciences 16 24%
Biochemistry, Genetics and Molecular Biology 12 18%
Medicine and Dentistry 8 12%
Nursing and Health Professions 4 6%
Sports and Recreations 3 4%
Other 7 10%
Unknown 17 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 July 2014.
All research outputs
#18,375,064
of 22,758,963 outputs
Outputs from PLOS ONE
#154,414
of 194,194 outputs
Outputs of similar age
#163,455
of 228,769 outputs
Outputs of similar age from PLOS ONE
#3,494
of 4,781 outputs
Altmetric has tracked 22,758,963 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 194,194 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.1. This one is in the 10th percentile – i.e., 10% of its peers scored the same or lower than it.
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We're also able to compare this research output to 4,781 others from the same source and published within six weeks on either side of this one. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.