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Contraction in cardiac endothelial cells contributes to changes in capillary dimensions following ischaemia and
1Molecular and Cellular Biology, Biomedical Sciences, Queen Mary and Westfield College, Mile End Road, E1 4NS, London, UK.
Insights
Cardiac capillary dimensions decrease during ischemia and reperfusion due to endothelial cell contraction. Stabilizing endothelial actin filaments prevented this reduction, suggesting a therapeutic target for reperfusion injury.
Area of Science:
- Cardiovascular Research
- Microcirculation Physiology
- Cellular Biology
Background:
- Ischemia followed by reperfusion leads to reduced cardiac capillary dimensions, suggesting constriction.
- The precise mechanism behind this dimensional change and its impact on microvascular injury remain under investigation.
Purpose of the Study:
- To test the hypothesis that endothelial cell contraction causes capillary dimensional changes during ischemia-reperfusion.
- To determine if modulating the endothelial cell contractile apparatus can mitigate microvascular reperfusion injury.
Main Methods:
- Isolated rat hearts were treated with phalloidin to stabilize endothelial actin filaments during ischemia.
- Capillary dimensions were quantified by measuring cross-sectional areas and membrane lengths.
- Scanning electron microscopy of resin casts examined structural changes in coronary capillaries after ischemia-reperfusion.
Main Results:
- Phalloidin treatment prevented the reduction in capillary dimensions during ischemia.
- Ischemia-reperfusion induced focal narrowings in capillaries, consistent with endothelial cell constriction.
- Structural analysis revealed constriction as the cause of reduced capillary dimensions.
Conclusions:
- The endothelial contractile apparatus plays a significant role in reducing cardiac capillary dimensions during ischemia-reperfusion.
- The cardiac capillary bed may exert greater local flow control than previously recognized.
- Modulating the actomyosin contractile system in cardiac capillary endothelial cells could reduce no-reflow injury.
Objective:
Ischaemia followed by reperfusion brings about a reduction in cardiac capillary cross-sectional dimensions which is consistent with constriction. The aim of this study was to test the hypothesis that the reduction in cardiac capillary dimensions that occurs in ischaemia and reperfusion is caused by endothelial cell contraction and that modulating the endothelial cell contractile apparatus reduces microvascular reperfusion injury.
Methods:
In isolated rat hearts we used phalloidin to stabilise the endothelial actin filaments in order to prevent the dimensional changes during ischaemia. The changes in endothelial cell dimensions were quantified by measuring whole capillary and luminal cross-sectional areas, abluminal and luminal membrane lengths. We have also used resin casts of the coronary vasculature coupled with scanning electron microscopy to examine the structural changes along the length of the capillaries in ischaemia-reperfusion.
Results:
We found that the reduction in capillary dimensions was prevented by the addition of phalloidin and, in the resin casts, that ischaemia-reperfusion cause focal narrowings along the capillaries which are consistent with constriction.
Conclusions:
(1) The endothelial contractile apparatus is involved in the reduction in cross-sectional dimensions. (2) This implies that the capillary bed may have a greater role in the local control of flow than was previously thought and that modulation of the actomyosin contractile system in cardiac capillary endothelial cells may be useful in reducing 'no reflow' injury which results from reperfusion.