Research ArticleVascular Biology

Angiophagy Prevents Early Embolus Washout But Recanalizes Microvessels Through Embolus Extravasation

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Science Translational Medicine  05 Mar 2014:
Vol. 6, Issue 226, pp. 226ra31
DOI: 10.1126/scitranslmed.3006585

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Beyond the Brain: Angiophagy Clears Clots in Other Organs, Too

Vessels in the body can be obstructed by tiny emboli, which are usually blood clots, but can also be cholesterol crystals or fragments of atherosclerotic plaques. Much like a bathroom drain, these clogged “pipes” can be cleared mechanically (hemodynamic forces) or biochemically (fibrinolysis). Now, Grutzendler and colleagues describe another possible clearance mechanism called angiophagy, where endothelial cells, which line the blood vessels, can actively remove clots from the vasculature.

Mice were given fibrin or cholesterol clots by a syringe to mimic the embolization process (where clots build up in the vasculature). Using sophisticated live-imaging techniques, Grutzendler et al. then peered into the blood vessels of mice to watch clot dynamics. They saw that endothelial cells were able to engulf these emboli in the microvasculature of the heart and the brain, causing them to exit the blood vessel entirely and allowing flow to resume in the vessel. The authors called this process “angiophagy” and noted that it occurred as early as 1 day after clot formation, with most clots being removed by day 4. Angiophagy also appeared to play a role in clot clearance from the mouse kidney, eye, and lung microvasculature, suggesting that this is a general means of extravasation and recanalization. Looking retrospectively at images of human retinal vessels, Grutzendler et al. were able to see microvascular emboli in the perivascular spaces, just outside the blood vessels, suggesting migration of the clot across the vessel wall.

Live imaging over time in several organ systems has shed light on the dynamics of this clot-clearing process. One limitation of angiophagy is that endothelial lamellipodia—while trying to engulf the clot for removal—apparently limit access of exogenous clot-busting drugs and endogenous fibrin-degrading enzymes to the emboli, thus reducing the early effectiveness of washout by other mechanisms. Nevertheless, knowing the time course of angiophagy in vivo in mice could help develop new anti-embolic drugs that could prevent widespread complications from medical procedures, aging, and disease.

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