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Increased mRNA Expression of Endothelial Adhesion Molecules and Proinflammatory Cytokines in the Type 2 Diabetic Heart Following Ischemia/Reperfusion Injury
Author(s) -
Pacheco Garrett S.,
Walker Corrine E.,
La Bonte Laura R.,
DavisGorman Grace,
Stahl Gregory L.,
McDonagh Paul F.
Publication year - 2007
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.21.6.a1145-a
Subject(s) - proinflammatory cytokine , cell adhesion molecule , medicine , reperfusion injury , intercellular adhesion molecule 1 , tumor necrosis factor alpha , endothelial activation , downregulation and upregulation , ischemia , inflammation , endocrinology , immunology , chemistry , biochemistry , gene
Restoration of blood flow is essential to preserve cardiac tissue viability and function, however it is now evident that cardiac reperfusion may lead to additional injury mediated largely by polymorphonuclear cells (PMNs). Recent work from our laboratory demonstrated that leukocyte accumulation in the coronary microcirculation may contribute to the severity of ischemic heart disease observed in the diabetic heart. PMN sequestration may be enhanced in the diabetic heart under situations of chronic endothelial cell activation, increased adhesion molecule, and/or other proinflammatory molecule expression. This observation of increased neutrophil sequestration in the myocardium following I/R led us to investigate the role of proinflammatory and endothelial adhesion molecule gene expression following I/R injury in the diabetic heart. Tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, P‐selectin, inducible nitric oxide synthase (iNOS), vascular cellular adhesion molecule (VCAM), and intercellular adhesion molecule (ICAM) were assessed by quantitative real time polymerase chain reaction (qRTPCR) in the at‐risk region of the left ventricle following 30min of ischemia and 120min of reperfusion. Zucker Diabetic Fatty (ZDF) rats demonstrated an upregulation of VCAM (10.9 fold change), ICAM (1.7 fold change), and TNF‐α (1.7 fold change) compared to Zucker Lean controls (ZLC). These results indicate a hyper‐responsiveness of the ZDF heart to I/R, which may contribute to enhanced PMN‐mediated I/R injury. Supported by AHA 0610018Z and NIH HLB 58859