Myocardial proteome analysis reveals reduced NOS inhibition and enhanced glycolytic capacity in areas of low local blood flow

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Tim LaussmannU K Decking

Abstract

In the heart, in situ local myocardial blood flow (MBF) varies greater than 10-fold between individual areas and displays a spatially heterogeneous pattern. To analyze its molecular basis, we analyzed protein expression of low and high flow samples (300 mg, <50% or >150% of mean MBF, each n=30) of six beagle dogs by 2-D polyacrylamide gel electrophoresis (380 +/- 78 spots/gel). In low flow samples, dimethylarginine dimethylaminohydrolase (DDAH1) was increased greatly (+377%, compared with high flow samples). This increase resulted in a 75% reduction of asymmetric dimethylarginine (ADMA), the potent endogenous inhibitor of NO synthase, whereas eNOS showed no difference. Low flow samples exhibited enhanced expression of GAPDH (+89%) and phosphoglycerate kinase (+100%), whereas hydroxyacyl-CoA dehydrogenase, electron transfer flavoprotein, myoglobin, and desmin were decreased. Assessing local MBF on different days within 2 weeks revealed a high degree of MBF stability (r2 > 0.79). Thus, stable differences in local MBF are associated with significant differences in local gene and protein expression. In low flow areas, the increased DDAH1 reduces ADMA concentration and NOS inhibition, which strongly suggests enhanced NO formation. L...Continue Reading

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Citations

Nov 5, 2004·Basic Research in Cardiology·Rainer SchulzGerd Heusch
Jun 14, 2005·Pharmacology & Therapeutics·R SchulzJ-L Balligand
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