PMID- 15851618
OWN - NLM
STAT- MEDLINE
DCOM- 20051228
LR  - 20171116
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 111
IP  - 16
DP  - 2005 Apr 26
TI  - Hyperhomocysteinemia, a cardiac metabolic disease: role of nitric oxide and the 
      p22phox subunit of NADPH oxidase.
PG  - 2112-8
AB  - BACKGROUND: Hyperhomocysteinemia (HHcy) is a reliable indicator of cardiovascular 
      disease, in part because of the production of superoxide and scavenging of nitric 
      oxide (NO). The present study assessed the impact of HHcy on the NO-dependent 
      control of cardiac O2 consumption and examined enzymatic sources of superoxide. 
      METHODS AND RESULTS: Rats and mice were fed methionine in drinking water for 5 to 
      9 weeks to increase plasma homocysteine, a process that did not cause significant 
      changes in hemodynamic function. The ability of the NO agonists bradykinin and 
      carbachol to reduce myocardial O2 consumption in vitro was impaired by 
      approximately 40% in methionine-fed rats, and this impairment was proportional to 
      their individual plasma homocysteine concentration. However, responses were 
      restored in the presence of ascorbic acid, tempol, and apocynin, which inhibits 
      NADPH oxidase assembly. Western blots showed no difference in Cu/Zn or Mn 
      superoxide dismutase, endothelial NO synthase, or inducible NO synthase protein, 
      but HHcy caused a 100% increase in the p22phox subunit of NADPH oxidase. Western 
      blots with plasma membrane-enriched fractions of cell lysate detected elevated 
      levels of p22phox, p67phox, and rac-1, which indicates increased oxidase 
      assembly. Finally, mice lacking a functional gp91phox subunit of NADPH oxidase 
      demonstrated normal NO-dependent regulation of myocardial O2 consumption after 
      methionine feeding. CONCLUSIONS: In HHcy, superoxide produced by NADPH oxidase 
      reduces the ability of NO to regulate mitochondrial function in the myocardium. 
      The severity of this effect is proportional to the increase in homocysteine.
FAU - Becker, Justin S
AU  - Becker JS
AD  - Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
FAU - Adler, Alexandra
AU  - Adler A
FAU - Schneeberger, Aaron
AU  - Schneeberger A
FAU - Huang, Harer
AU  - Huang H
FAU - Wang, Zipping
AU  - Wang Z
FAU - Walsh, Erin
AU  - Walsh E
FAU - Koller, Akos
AU  - Koller A
FAU - Hintze, Thomas H
AU  - Hintze TH
LA  - eng
GR  - 61290/PHS HHS/United States
GR  - HL 46813/HL/NHLBI NIH HHS/United States
GR  - P0-1 HL 43023/HL/NHLBI NIH HHS/United States
GR  - R0-1 HL 50142/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Phosphoproteins)
RN  - 11062-77-4 (Superoxides)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - AE28F7PNPL (Methionine)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (CYBA protein, human)
SB  - IM
CIN - Circulation. 2005 Oct 11;112(15):e266. PMID: 16216970
MH  - Animals
MH  - Heart Diseases/*metabolism
MH  - Hyperhomocysteinemia/chemically induced/enzymology/*metabolism
MH  - Male
MH  - Membrane Transport Proteins/*biosynthesis
MH  - Methionine
MH  - Mice
MH  - Mice, Knockout
MH  - Myocardium/enzymology/metabolism
MH  - NADPH Oxidases/*biosynthesis/metabolism
MH  - Nitric Oxide/*metabolism
MH  - Oxygen Consumption
MH  - Phosphoproteins/*biosynthesis
MH  - Rats
MH  - Rats, Wistar
MH  - Superoxides/metabolism
MH  - Up-Regulation
EDAT- 2005/04/27 09:00
MHDA- 2005/12/29 09:00
CRDT- 2005/04/27 09:00
PHST- 2005/04/27 09:00 [pubmed]
PHST- 2005/12/29 09:00 [medline]
PHST- 2005/04/27 09:00 [entrez]
AID - 111/16/2112 [pii]
AID - 10.1161/01.CIR.0000162506.61443.15 [doi]
PST - ppublish
SO  - Circulation. 2005 Apr 26;111(16):2112-8. doi: 10.1161/01.CIR.0000162506.61443.15.