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Evidence that fatty acyl CoA synthetase is a mediator of ischemia/reperfusion injury (I/R) in the rat
Author(s) -
Blakeman Nina,
Chen Qian,
Young Lindon,
Weis Margaret
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.821.32
Subject(s) - reperfusion injury , mediator , ischemia , chemistry , pharmacology , biochemistry , medicine
Decreased NO synthesis during ischemia is thought to facilitate surface expression of cell adhesion molecules such as pCAM, contributing to I/R injury. Earlier, we showed that Triacsin C (TriC), a long chain fatty acyl CoA synthetase inhibitor, increased NO release in cultured human and rat vascular endothelial cells and isolated rat aortic segments, leading us to hypothesize that TriC would increase NO and reduce leukocyte transmigration during experimental ischemia. Using the rat ischemic hind‐limb model instrumented with NO probes (WPI Instruments), we measured the difference in NO concentration between the normoxic and ischemic limbs in TriC or vehicle treated animals. The results are shown:Treatment Control Ischemia ReperfusionVehicle 0.54±2.1 nM −195±8.4 nM 11 ± 7.5 nM TriC 2.3±10 nM −83±4.3 nM * 130 ±3.1 nM ** = p<0.05 vs vehicle; n=5 for each groupLeukocyte adhesion, rolling and transmigration were evaluated by intravital microscopy in the rat mesenteric vasculature of TriC or vehicle treated animals. The results (leukocytes/min) are summarized:Vehicle n = 3 TriC n = 4Rolling t 0 13 ±3 11±2 NS t 120 min 48±6 16±5 p<0.001Adhesion t 0 1±1 1±1 NS t 120 min 9±1 3±1 p<0.001Transmigration t 0 1±1 1±1 NS t 120 min 6±1 2±1 p<0.001These results strongly support our hypothesis, and suggest that long chain fatty acyl CoA synthetase is a key enzyme in governing eNOS activity during I/R. Supported by NIH R21‐AG028901 (Weis).