{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:50:38Z","timestamp":1791600638348,"version":"4.3.4"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Artificial Organs"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Among patients reliant on continuous\u2010flow (CF) mechanical circulatory support devices, bleeding is primarily caused by an acquired von Willebrand factor (vWF) deficiency, precipitated by the high shear stress and diminished pulsatility inherent to these systems. However, despite its clinical significance, the relationship between these devices' flow modes and the development of vWF defects remains poorly investigated. Herein, we conducted molecular dynamic (MD) simulations and in\u00a0vivo validation to investigate this relationship.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study involved the analysis of a novel flow sensory mechanism of the vWF molecule, elucidating the inherent relationship through an integrated approach including simulations, an in\u00a0vitro flow platform, and experiments involving rats undergoing venoarterial extracorporeal membrane oxygenation (V\u2010A ECMO).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MD simulations demonstrated that the vWF\u2010A dimer underwent significant retraction under pulsatile\u2010flow (PF) conditions, indicating an autoinhibitory effect on enzymatic cleavage. Conversely, under CF conditions, we observed a pronounced reduction in circulating vWF levels and a decrease in endothelial cell vWF secretion compared with both the PF and sham groups of rats undergoing V\u2010A ECMO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings underscore the critical importance of pulsatility in the design of next\u2010generation blood pumps and highlight the potential of our novel rat model in future investigations of the physiological and molecular responses to different blood flow patterns during V\u2010A ECMO.<\/jats:p>\n                  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