Fluid Shear Attenuates Endothelial Pseudopodia Formation into the Capillary Lumen

Abstract

Endothelial cells have the ability to undergo morphological shape changes, including projection of cytoplasmic pseudopodia into the capillary lumen. These cytoplasmic projections significantly influence the hemodynamic resistance to blood flow. To examine mechanotransduction mechanisms, we investigated in vivo the hemodynamic conditions in capillaries that control endothelial pseudopod formation. Capillaries in rat skeletal muscle were fixed under carefully controlled perfusion conditions. The formation of endothelial pseudopodia were observed in cross-sections with electron microscopy and quantified with differential interference contrast microscopy under physiological, stasis, and reperfusion flow conditions. Application of physiological levels of fluid flow prevents capillary endothelium to project pseudopodia into the capillary lumen. Reduction of fluid flow to near zero promotes the incidence of pseudopod projection from 5% to 55% of capillaries. After capillary pseudopodia have formed under static conditions, about one-half retract upon restoration of fluid flow. The presence of red blood cells in the capillary lumen prevents pseudopod formation. The results suggest that there is a mechanism that serves to control cytoplasmic projections in capillary endothelium that is under the control of hemodynamic fluid stress. Investigation of pseudopodia growth on endothelial cells may be significant in understanding capillary obstruction in cardiovascular diseases.