Induction of autophagy markers is associated with attenuation of miR-133a in diabetic heart failure patients undergoing mechanical unloading

Shyam Sundar Nandi, Michael J. Duryee, Hamid R. Shahshahan, Geoffrey Milton Thiele, Daniel R Anderson, Paras Kumar Mishra

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Autophagy is ubiquitous in all forms of heart failure and cardioprotective miR-133a is attenuated in human heart failure. Previous reports from heart failure patients undergoing left ventricular assist device (LVAD) implantation demonstrated that autophagy is upregulated in the LV of the failing human heart. Studies in the murine model show that diabetes downregulates miR-133a. However, the role of miR-133a in the regulation of autophagy in diabetic hearts is unclear. We tested the hypothesis that diabetes exacerbates cardiac autophagy by inhibiting miR-133a in heart failure patients undergoing LVAD implantation. The miRNA assay was performed on the LV of 15 diabetic (D) and 6 non-diabetic (ND) heart failure patients undergoing LVAD implantation. Four ND with highly upregulated and 5 D with highly downregulated miR-133a were analyzed for autophagy markers (Beclin1, LC3B, ATG3) and their upstream regulators (mTOR and AMPK), and hypertrophy marker (beta-myosin heavy chain) by RT-qPCR, Western blotting and immunofluorescence. Our results demonstrate that attenuation of miR-133a in diabetic hearts is associated with the induction of autophagy and hypertrophy, and suppression of mTOR without appreciable difference in AMPK activity. In conclusion, attenuation of miR-133a contributes to the exacerbation of diabetes mediated cardiac autophagy and hypertrophy in heart failure patients undergoing LVAD implantation.

Original languageEnglish (US)
Pages (from-to)683-696
Number of pages14
JournalAmerican Journal of Translational Research
Volume7
Issue number4
StatePublished - Jan 1 2015

Fingerprint

Autophagy
Unloading
Heart Failure
Heart-Assist Devices
Left ventricular assist devices
AMP-Activated Protein Kinases
Medical problems
Hypertrophy
Down-Regulation
Ventricular Myosins
Myosin Heavy Chains
Cardiomegaly
MicroRNAs
Fluorescent Antibody Technique
Western Blotting
Assays

Keywords

  • Ampk
  • Beclin1
  • Hypertrophy
  • LC3B
  • LVAD
  • MTOR
  • Milrinone

ASJC Scopus subject areas

  • Molecular Medicine
  • Clinical Biochemistry
  • Cancer Research

Cite this

@article{d0ff8893e19d45f9af994e4296d154a3,
title = "Induction of autophagy markers is associated with attenuation of miR-133a in diabetic heart failure patients undergoing mechanical unloading",
abstract = "Autophagy is ubiquitous in all forms of heart failure and cardioprotective miR-133a is attenuated in human heart failure. Previous reports from heart failure patients undergoing left ventricular assist device (LVAD) implantation demonstrated that autophagy is upregulated in the LV of the failing human heart. Studies in the murine model show that diabetes downregulates miR-133a. However, the role of miR-133a in the regulation of autophagy in diabetic hearts is unclear. We tested the hypothesis that diabetes exacerbates cardiac autophagy by inhibiting miR-133a in heart failure patients undergoing LVAD implantation. The miRNA assay was performed on the LV of 15 diabetic (D) and 6 non-diabetic (ND) heart failure patients undergoing LVAD implantation. Four ND with highly upregulated and 5 D with highly downregulated miR-133a were analyzed for autophagy markers (Beclin1, LC3B, ATG3) and their upstream regulators (mTOR and AMPK), and hypertrophy marker (beta-myosin heavy chain) by RT-qPCR, Western blotting and immunofluorescence. Our results demonstrate that attenuation of miR-133a in diabetic hearts is associated with the induction of autophagy and hypertrophy, and suppression of mTOR without appreciable difference in AMPK activity. In conclusion, attenuation of miR-133a contributes to the exacerbation of diabetes mediated cardiac autophagy and hypertrophy in heart failure patients undergoing LVAD implantation.",
keywords = "Ampk, Beclin1, Hypertrophy, LC3B, LVAD, MTOR, Milrinone",
author = "Nandi, {Shyam Sundar} and Duryee, {Michael J.} and Shahshahan, {Hamid R.} and Thiele, {Geoffrey Milton} and Anderson, {Daniel R} and Mishra, {Paras Kumar}",
year = "2015",
month = "1",
day = "1",
language = "English (US)",
volume = "7",
pages = "683--696",
journal = "American Journal of Translational Research",
issn = "1943-8141",
publisher = "e-Century Publishing Corporation",
number = "4",

}

TY - JOUR

T1 - Induction of autophagy markers is associated with attenuation of miR-133a in diabetic heart failure patients undergoing mechanical unloading

AU - Nandi, Shyam Sundar

AU - Duryee, Michael J.

AU - Shahshahan, Hamid R.

AU - Thiele, Geoffrey Milton

AU - Anderson, Daniel R

AU - Mishra, Paras Kumar

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Autophagy is ubiquitous in all forms of heart failure and cardioprotective miR-133a is attenuated in human heart failure. Previous reports from heart failure patients undergoing left ventricular assist device (LVAD) implantation demonstrated that autophagy is upregulated in the LV of the failing human heart. Studies in the murine model show that diabetes downregulates miR-133a. However, the role of miR-133a in the regulation of autophagy in diabetic hearts is unclear. We tested the hypothesis that diabetes exacerbates cardiac autophagy by inhibiting miR-133a in heart failure patients undergoing LVAD implantation. The miRNA assay was performed on the LV of 15 diabetic (D) and 6 non-diabetic (ND) heart failure patients undergoing LVAD implantation. Four ND with highly upregulated and 5 D with highly downregulated miR-133a were analyzed for autophagy markers (Beclin1, LC3B, ATG3) and their upstream regulators (mTOR and AMPK), and hypertrophy marker (beta-myosin heavy chain) by RT-qPCR, Western blotting and immunofluorescence. Our results demonstrate that attenuation of miR-133a in diabetic hearts is associated with the induction of autophagy and hypertrophy, and suppression of mTOR without appreciable difference in AMPK activity. In conclusion, attenuation of miR-133a contributes to the exacerbation of diabetes mediated cardiac autophagy and hypertrophy in heart failure patients undergoing LVAD implantation.

AB - Autophagy is ubiquitous in all forms of heart failure and cardioprotective miR-133a is attenuated in human heart failure. Previous reports from heart failure patients undergoing left ventricular assist device (LVAD) implantation demonstrated that autophagy is upregulated in the LV of the failing human heart. Studies in the murine model show that diabetes downregulates miR-133a. However, the role of miR-133a in the regulation of autophagy in diabetic hearts is unclear. We tested the hypothesis that diabetes exacerbates cardiac autophagy by inhibiting miR-133a in heart failure patients undergoing LVAD implantation. The miRNA assay was performed on the LV of 15 diabetic (D) and 6 non-diabetic (ND) heart failure patients undergoing LVAD implantation. Four ND with highly upregulated and 5 D with highly downregulated miR-133a were analyzed for autophagy markers (Beclin1, LC3B, ATG3) and their upstream regulators (mTOR and AMPK), and hypertrophy marker (beta-myosin heavy chain) by RT-qPCR, Western blotting and immunofluorescence. Our results demonstrate that attenuation of miR-133a in diabetic hearts is associated with the induction of autophagy and hypertrophy, and suppression of mTOR without appreciable difference in AMPK activity. In conclusion, attenuation of miR-133a contributes to the exacerbation of diabetes mediated cardiac autophagy and hypertrophy in heart failure patients undergoing LVAD implantation.

KW - Ampk

KW - Beclin1

KW - Hypertrophy

KW - LC3B

KW - LVAD

KW - MTOR

KW - Milrinone

UR - http://www.scopus.com/inward/record.url?scp=84930386412&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930386412&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:84930386412

VL - 7

SP - 683

EP - 696

JO - American Journal of Translational Research

JF - American Journal of Translational Research

SN - 1943-8141

IS - 4

ER -