PMID- 19669742
OWN - NLM
STAT- MEDLINE
DCOM- 20091222
LR  - 20211020
IS  - 1559-0283 (Electronic)
IS  - 1085-9195 (Print)
IS  - 1085-9195 (Linking)
VI  - 55
IP  - 3
DP  - 2009
TI  - MicroRNAs are involved in homocysteine-induced cardiac remodeling.
PG  - 153-62
LID - 10.1007/s12013-009-9063-6 [doi]
AB  - 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.
FAU - Mishra, Paras K
AU  - Mishra PK
AD  - Department of Physiology & Biophysics, University of Louisville, School of 
      Medicine, A-1215, 500 South Preston Street, Louisville, KY, 40202, USA.
FAU - Tyagi, Neetu
AU  - Tyagi N
FAU - Kundu, Soumi
AU  - Kundu S
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - R01 HL074185/HL/NHLBI NIH HHS/United States
GR  - R01 HL088012-03/HL/NHLBI NIH HHS/United States
GR  - R01 HL071010/HL/NHLBI NIH HHS/United States
GR  - R01 NS051568/NS/NINDS NIH HHS/United States
GR  - R01 NS051568-03/NS/NINDS NIH HHS/United States
GR  - R01 HL071010-07/HL/NHLBI NIH HHS/United States
GR  - HL-88012/HL/NHLBI NIH HHS/United States
GR  - R01 HL088012/HL/NHLBI NIH HHS/United States
GR  - R01 HL074185-06/HL/NHLBI NIH HHS/United States
GR  - HL 71010/HL/NHLBI NIH HHS/United States
GR  - HL-74185/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090811
PL  - United States
TA  - Cell Biochem Biophys
JT  - Cell biochemistry and biophysics
JID - 9701934
RN  - 0 (MicroRNAs)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.- (Nox4 protein, mouse)
RN  - EC 3.1.26.3 (Ribonuclease III)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line
MH  - Gene Expression Profiling
MH  - Homocysteine/metabolism/*pharmacology
MH  - Hyperhomocysteinemia/*genetics/*metabolism
MH  - Matrix Metalloproteinases/genetics/metabolism
MH  - Mice
MH  - *MicroRNAs
MH  - Myocytes, Cardiac/*physiology
MH  - NADPH Oxidase 4
MH  - NADPH Oxidases/genetics/metabolism
MH  - Regeneration/*drug effects
MH  - Ribonuclease III
MH  - Tissue Inhibitor of Metalloproteinases/genetics/metabolism
PMC - PMC2863043
MID - NIHMS182795
EDAT- 2009/08/12 09:00
MHDA- 2009/12/23 06:00
PMCR- 2010/05/04
CRDT- 2009/08/12 09:00
PHST- 2009/06/02 00:00 [received]
PHST- 2009/07/20 00:00 [accepted]
PHST- 2009/08/12 09:00 [entrez]
PHST- 2009/08/12 09:00 [pubmed]
PHST- 2009/12/23 06:00 [medline]
PHST- 2010/05/04 00:00 [pmc-release]
AID - 10.1007/s12013-009-9063-6 [doi]
PST - ppublish
SO  - Cell Biochem Biophys. 2009;55(3):153-62. doi: 10.1007/s12013-009-9063-6. Epub 
      2009 Aug 11.