PMID- 17178594
OWN - NLM
STAT- MEDLINE
DCOM- 20071126
LR  - 20191110
IS  - 1381-3455 (Print)
IS  - 1744-4160 (Electronic)
IS  - 1381-3455 (Linking)
VI  - 112
IP  - 4-5
DP  - 2006 Oct-Dec
TI  - Arrhythmia and neuronal/endothelial myocyte uncoupling in hyperhomocysteinemia.
PG  - 219-27
AB  - Elevated levels of homocysteine (Hcy) known as hyperhomocysteinemia (HHcy) are 
      associated with arrhythmogenesis and sudden cardiac death (SCD). Hcy decreases 
      constitutive neuronal and endothelial nitric oxide (NO), and cardiac diastolic 
      relaxation. Hcy increases the iNOS/NO, peroxynitrite, mitochondrial NADPH 
      oxidase, and suppresses superoxide dismutase (SOD) and redoxins. Hcy activates 
      matrix metalloproteinase (MMP), disrupts connexin-43 and increases 
      collagen/elastin ratio. The disruption of connexin-43 and accumulation of 
      collagen (fibrosis) disrupt the normal pattern of cardiac conduction and 
      attenuate NO transport from endothelium to myocyte (E-M) causing E-M uncoupling, 
      leading to a pro-arrhythmic environment. The goal of this review is to elaborate 
      the mechanism of Hcy-mediated iNOS/NO in E-M uncoupling and SCD. It is known that 
      Hcy creates arrhythmogenic substrates (i.e. increase in collagen/elastin ratio 
      and disruption in connexin-43) and exacerbates heart failure during chronic 
      volume overload. Also, Hcy behaves as an agonist to N-methyl-D-aspartate (NMDA, 
      an excitatory neurotransmitter) receptor-1, and blockade of NMDA-R1 reduces the 
      increase in heart rate-evoked by NMDA-analog and reduces SCD. This review suggest 
      that Hcy increases iNOS/NO, superoxide, metalloproteinase activity, and disrupts 
      connexin-43, exacerbates endothelial-myocyte uncoupling and cardiac failure 
      secondary to inducing NMDA-R1.
FAU - Rosenberger, Dorothea
AU  - Rosenberger D
AD  - Department of Physiology and Biophysics, University of Louisville School of 
      Medicine, Louisville, Kentucky 40202, USA.
FAU - Moshal, Karni S
AU  - Moshal KS
FAU - Kartha, Ganesh K
AU  - Kartha GK
FAU - Tyagi, Neetu
AU  - Tyagi N
FAU - Sen, Utpal
AU  - Sen U
FAU - Lominadze, David
AU  - Lominadze D
FAU - Maldonado, Claudio
AU  - Maldonado C
FAU - Roberts, Andrew M
AU  - Roberts AM
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - R01 HL074185/HL/NHLBI NIH HHS/United States
GR  - R01 HL080394-01A2/HL/NHLBI NIH HHS/United States
GR  - R01 HL080394/HL/NHLBI NIH HHS/United States
GR  - R01 HL071010/HL/NHLBI NIH HHS/United States
GR  - HL-74185/HL/NHLBI NIH HHS/United States
GR  - HL-71010/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - England
TA  - Arch Physiol Biochem
JT  - Archives of physiology and biochemistry
JID - 9510153
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9007-34-5 (Collagen)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Arrhythmias, Cardiac/etiology/*physiopathology
MH  - Collagen/metabolism
MH  - Death, Sudden, Cardiac/etiology
MH  - Endothelium, Vascular/*metabolism/pathology
MH  - Fibrosis/metabolism/pathology
MH  - Heart Conduction System
MH  - Heart Rate
MH  - Homocysteine/blood
MH  - Humans
MH  - Hyperhomocysteinemia/complications/*physiopathology
MH  - Matrix Metalloproteinases/*metabolism
MH  - Myocytes, Cardiac/*physiology
MH  - Nitric Oxide/deficiency
MH  - Nitric Oxide Synthase Type I
MH  - *Nitric Oxide Synthase Type III
PMC - PMC3182485
MID - NIHMS169034
EDAT- 2006/12/21 09:00
MHDA- 2007/12/06 09:00
PMCR- 2011/09/29
CRDT- 2006/12/21 09:00
PHST- 2006/12/21 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2006/12/21 09:00 [entrez]
PHST- 2011/09/29 00:00 [pmc-release]
AID - T32R910N13656231 [pii]
AID - 10.1080/13813450601093443 [doi]
PST - ppublish
SO  - Arch Physiol Biochem. 2006 Oct-Dec;112(4-5):219-27. doi: 
      10.1080/13813450601093443.