MicroRNAs Are Involved in Homocysteine-Induced Cardiac Remodeling

Paras K. Mishra, Neetu Tyagi, Soumi Kundu, Suresh C. Tyagi

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Elevated level of homocysteine (Hcy) called hyperhomocysteinemia (HHcy) is one of the major risk factors for chronic heart failure. Although the role of Hcy in cardiac remodeling is documented, the regulatory mechanism involved therein is still nebulous. MicroRNAs (miRNAs) and dicer have been implicated in regulation of cardiovascular diseases. Dicer is the only known enzyme involved in miRNA maturation. We investigated the involvement of dicer and miRNA in Hcy-induced cardiac remodeling. HL-1 cardiomyocytes were cultured in different doses of Hcy. Total RNA was isolated and RT-PCR and real-time PCR was performed for dicer, MMP-2,-9, TIMP-1,-3, and NOX-4. MiRNA microarray was used for analyzing the differential expression of miRNAs. Individual miRNA assay was also done. Western blotting was used to assess the MMP-9 expression in HHcy cardiomyocytes. The RT-PCR results suggest that dicer expression is enhanced in HHcy cardiomyocytes suggesting its involvement in cardiac remodeling caused due to high dose of Hcy. On the other hand, high dose of Hcy increased NOX-4 expression, a marker for oxidative stress. Additionally, HHcy cardiomyocytes showed elevated levels of MMP-2,-9 and TIMP-1,-3, and reduced expression of TIMP-4, suggesting cardiac remodeling due to oxidative stress. The miRNA microarray assay revealed differential expression of 11 miRNAs and among them miR-188 show dramatic downregulation. These findings suggest that dicer and miRNAs especially miR-188 are involved in Hcy-induced cardiac remodeling.

Original languageEnglish (US)
Pages (from-to)153-162
Number of pages10
JournalCell Biochemistry and Biophysics
Volume55
Issue number3
DOIs
StatePublished - Aug 11 2009

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Homocysteine
MicroRNAs
Hyperhomocysteinemia
Cardiac Myocytes
Matrix Metalloproteinases
Tissue Inhibitor of Metalloproteinase-3
Tissue Inhibitor of Metalloproteinase-1
Oxidative stress
Microarrays
Assays
Oxidative Stress
Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Cardiovascular Diseases
Down-Regulation
Heart Failure
Western Blotting
RNA
Enzymes

Keywords

  • Congestive heart failure
  • Dicer
  • Extracellular matrix remodeling
  • Hyperhomocysteinemia
  • Matrix-metalloproteinase (MMP)
  • MicroRNA
  • Tissue inhibitors of metalloproteinase (TIMP)

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

MicroRNAs Are Involved in Homocysteine-Induced Cardiac Remodeling. / Mishra, Paras K.; Tyagi, Neetu; Kundu, Soumi; Tyagi, Suresh C.

In: Cell Biochemistry and Biophysics, Vol. 55, No. 3, 11.08.2009, p. 153-162.

Research output: Contribution to journalArticle

Mishra, Paras K. ; Tyagi, Neetu ; Kundu, Soumi ; Tyagi, Suresh C. / MicroRNAs Are Involved in Homocysteine-Induced Cardiac Remodeling. In: Cell Biochemistry and Biophysics. 2009 ; Vol. 55, No. 3. pp. 153-162.
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