Angiophagy prevents early embolus washout but recanalizes microvessels through embolus extravasation. Sci Transl Med 2014 Mar 05;6(226):226ra31
Date
03/07/2014Pubmed ID
24598589DOI
10.1126/scitranslmed.3006585Scopus ID
2-s2.0-84897543651 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
Occlusion of the microvasculature by blood clots, atheromatous fragments, or circulating debris is a frequent phenomenon in most human organs. Emboli are cleared from the microvasculature by hemodynamic pressure and the fibrinolytic system. An alternative mechanism of clearance is angiophagy, in which emboli are engulfed by the endothelium and translocate through the microvascular wall. We report that endothelial lamellipodia surround emboli within hours of occlusion, markedly reducing hemodynamic washout and tissue plasminogen activator-mediated fibrinolysis in mice. Over the next few days, emboli are completely engulfed by the endothelium and extravasated into the perivascular space, leading to vessel recanalization and blood flow reestablishment. We find that this mechanism is not limited to the brain, as previously thought, but also occurs in the heart, retina, kidney, and lung. In the lung, emboli cross into the alveolar space where they are degraded by macrophages, whereas in the kidney, they enter the renal tubules, constituting potential routes for permanent removal of circulating debris. Retina photography and angiography in patients with embolic occlusions provide indirect evidence suggesting that angiophagy may also occur in humans. Thus, angiophagy appears to be a ubiquitous mechanism that could be a therapeutic target with broad implications in vascular occlusive disorders. Given its biphasic nature-initially causing embolus retention, and subsequently driving embolus extravasation-it is likely that different therapeutic strategies will be required during these distinct post-occlusion time windows.
Author List
Grutzendler J, Murikinati S, Hiner B, Ji L, Lam CK, Yoo T, Gupta S, Hafler BP, Adelman RA, Yuan P, Rodriguez GMESH terms used to index this publication - Major topics in bold
AnimalsBrain
Cerebrovascular Circulation
Coronary Circulation
Embolism
Fibrin
Fibrinolysis
Fundus Oculi
Green Fluorescent Proteins
Hemodynamics
Humans
Kidney Tubules
Lung
Macrophages
Mice
Mice, Transgenic
Microcirculation
Microglia
Microscopy, Electron, Transmission
Microvessels
Monocytes
Phagocytosis
Retina
Retinal Vessels
Thrombosis
