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Time course of coronary vascular endothelial adhesion molecule expression during reperfusion of the ischemic feline
A S Weyrich1, M Buerke, K H Albertine
1Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-6799.
Insights
This study shows sequential expression of P-selectin and ICAM-1 in feline heart reperfusion, coordinating neutrophil trafficking. E-selectin expression was minimal within 270 minutes post-reperfusion.
Area of Science:
- Cardiovascular Biology
- Immunology
- Pathophysiology
Background:
- Myocardial ischemia and reperfusion injury involve complex cellular and molecular events.
- Endothelial cell adhesion molecules play a critical role in inflammatory responses following ischemia.
- Understanding the temporal expression of these molecules is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the time course of endothelial P-selectin, ICAM-1, and E-selectin expression in a feline model of myocardial ischemia and reperfusion.
- To correlate the expression patterns of these adhesion molecules with the inflammatory response during reperfusion.
Main Methods:
- A feline model was used, subjecting cats to 90 minutes of myocardial ischemia followed by varying reperfusion periods (0-270 minutes).
- Immunohistochemistry with specific monoclonal antibodies (mAbs) was employed to localize P-selectin, ICAM-1, and E-selectin in the coronary vasculature.
- Quantification of positive staining in coronary venules assessed the expression levels and distribution of these molecules.
Main Results:
- P-selectin expression peaked at 20 minutes post-reperfusion and gradually declined.
- ICAM-1 expression was modest early on but significantly increased at 150 and 270 minutes of reperfusion.
- E-selectin expression was minimal, observed only at later time points (150 and 270 minutes), suggesting a delayed response.
Conclusions:
- The study demonstrates a sequential expression pattern of P-selectin and ICAM-1 during myocardial ischemia and reperfusion.
- The temporal expression of P-selectin and ICAM-1 may orchestrate neutrophil recruitment in the early stages of reperfusion injury.
- E-selectin appears to play a less significant role in the early phase of reperfusion within the studied timeframe.
Abstract:
The time course of endothelial P-selectin, ICAM-1, and E-selectin expression was studied in a feline model of myocardial ischemia and reperfusion. Cats were subjected to 90 min of myocardial ischemia followed by 0, 10, 20, 60, 150, or 270 min of reperfusion. At the end of reperfusion, the coronary vasculature was examined immunohistochemically to localize monoclonal antibodies (mAbs) PB1.3, RR1/1, and Cy1787 directed against P-selectin, ICAM-1, and E-selectin, respectively. Immunohistochemical localization for P-selectin, recognized by mAb PB1.3, was maximally expressed 20 min after reperfusion in 60 +/- 6% of coronary venules (P < 0.05 compared to non-reperfused controls), and covered 59 +/- 3% of the endothelial cell perimeter of immunostained coronary venules. Immunolocalization of mAb PB1.3 gradually declined at 60, 150, and 270 min of reperfusion. Immunohistochemical localization of mAb RR1/1 (anti-ICAM-1) in endothelial cells of coronary venules was observed to a modest extent in non-ischemic myocardium and at 10, 20, and 60 min of reperfusion, but was significantly increased following 150 and 270 min of reperfusion (P < 0.05 compared non-reperfused controls). At 270 min post-reperfusion, mAb RR1/1 was seen in 50 +/- 4% of coronary venules. Endothelial immunolocalization of mAb Cy1787 (anti-E-selectin) was only observed in 13 +/- 1 and 14 +/- 3% of coronary venules after 150 and 270 min of reperfusion, respectively, suggesting that pronounced expression of E-selectin does not occur within 270 min after reperfusion. These results demonstrate sequential expression of three major endothelial cell adherence molecules in situ following myocardial ischemia and reperfusion. The timing of endothelial cell expressed P-selectin and ICAM-1 could coordinate neutrophil trafficking during the early stages of reperfusion.