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Article
Triacsin C, a Fatty Acyl CoA Synthetase Inhibitor, Improves Cardiac Performance Following Global Ischemia
American Journal of Biomedical Sciences
  • Nina Blakeman
  • Qian Chen
  • Jasmine Tolson
  • Brian Rueter
  • Brian Diaz
  • Brenan Casey
  • Lindon H. Young, Philadelphia College of Osteopathic Medicine
  • Margaret T. Weis
Document Type
Article
Publication Date
1-1-2012
Abstract
The role of fatty acyl CoA synthetase (FACS) in ischemia/reperfusion (I/R) injury has not been well established. Our earlier studies showed that triacsin C, a selective FACS inhibitor, decreases endothelial nitric oxide synthase (eNOS) palmitoylation and increases nitric oxide (NO) in cultured human coronary endothelial cells. In the present study, we tested the hypothesis that triacsin C would reduce infarct size and improve post-reperfusion cardiac function by increasing vascular NO. In isolated rat hearts, triacsin C, given during the first 5 minutes of reperfusion, significantly reduced infarct size and attenuated cardiac dysfunction during reperfusion. N G -nitro-L-arginine methyl ester (L-NAME, a non-selective NOS inhibitor, 50 µM) completely abolished the protective effects of triacsin C. In the ischemic hind limb model, triacsin C significantly increased intravascular NO concentration during reperfusion, an effect that was blocked by LNAME or S-methyl-L-thiocitrulline (SMTC, a selective neuronal NOS inhibitor), but not by 1400W (a highly selective iNOS inhibitor). Lastly, triacsin C significantly reduced L-NAME induced leukocyte rolling, adhesion, and transmigration in rat mesenteric circulation, as measured by intravital microscopy. In summary, this study provides novel evidence showing that triacsin C reduces myocardial infarct size, attenuates loss of post-reperfusion cardiac function, increases intravascular NO concentration and inhibits leukocyte recruitment. These pharmacologic properties suggest that triacsin C may be useful as an adjunct to standard thrombolytic/anti-platelet pharmacotherapy of myocardial infarction.
Comments

This article was published in American Journal of Biomedical Sciences, Volume 4, Number 3, 2012, pages 249-261.

The published version is available at http://dx.doi.org/10.5099/aj120300252.

Copyright © 2012 NWPII

Citation Information
Nina Blakeman, Qian Chen, Jasmine Tolson, Brian Rueter, et al.. "Triacsin C, a Fatty Acyl CoA Synthetase Inhibitor, Improves Cardiac Performance Following Global Ischemia" American Journal of Biomedical Sciences Vol. 4 Iss. 3 (2012) p. 249 - 261
Available at: http://works.bepress.com/qian_chen/12/