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As Impella ® microaxial pumps achieve very high shear rates we investigated the prevalence of AVWS in this patient cohort. In LVAD patients, shear stress-induced conformational change and subsequent proteolytic cleavage is the proposed mechanism for AVWS. The latter group, for example, comprises patients with aortic valve stenosis and the increasing cohort of permanent left ventricular assist device (LVAD) patients. As triple therapy predisposes to bleeding complications, distinct therapy options depending on the underlying mechanism would be desirable.Īcquired von Willebrand syndrome (AVWS) is a bleeding disorder caused by structural or functional alterations of von Willebrand factor (VWF) commonly attributable to an underlying disease, such as hematological and autoimmune disorders and cardiovascular diseases. Consequently, dual antiplatelet therapy as well as systemic anticoagulation to prevent clotting of the device is indispensable on mechanical support. As coronary ischemia is a major cause of CS, rapid revascularization is the treatment of choice. Different Impella ® devices are available varying in size and maximum flow capabilities. Blood is drawn from the left ventricle cavity and expelled above the aortic valve into the ascending aorta. Microaxial pumps can easily be implanted under fluoroscopic guidance directly in the cath lab via transfemoral access. Īmongst others, options of MCS comprise veno-arterial extracorporeal membrane oxygenation (va-ECMO) bypassing the right and left ventricle and microaxial pump for left ventricular unloading such as the Impella ® family. Hence, current guidelines recommend the early use of mechanical circulatory support (MCS) in refractory CS. Mortality of cardiogenic shock (CS) patients remains high despite improvement of intensive care strategies. Roles Funding acquisition, Resources, Supervision, Validation, Writing – review & editing Roles Conceptualization, Funding acquisition, Supervision, Writing – review & editing Roles Data curation, Formal analysis, Supervision, Validation, Visualization, Writing – review & editing Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Writing – review & editing Roles Data curation, Investigation, Resources, Supervision, Writing – review & editing Roles Data curation, Funding acquisition, Investigation, Writing – review & editing Roles Conceptualization, Data curation, Investigation, Writing – review & editing Roles Conceptualization, Funding acquisition, Investigation, Supervision, Writing – review & editing This direct involvement of Aurora B in SAC signaling may maintain SAC signaling even after Mps1 activity in the kinetochore is lowered.Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editingĪffiliation: Hannover Medical School, Department of Cardiology and Angiology, Cardiac Arrest Center and Advanced Heart Failure Unit, Hannover, Germany
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These and other data show that Aurora B cooperates with Bub1 to promote MCC production, but only after Mps1 licenses Bub1 recruitment to the kinetochore. 13, 14, 15, 16 Importantly, Bub1 must recruit both Mad1 and Cdc20 for this ectopic signaling activity. Using the ectopic SAC activation (eSAC) system, we find that the conditional dimerization of Aurora B in budding yeast and an Aurora B recruitment domain in HeLa cells with either Bub1 or Mad1, but not the phosphodomain of Spc105/KNL1, leads to ectopic MCC production and mitotic arrest. 9, 10, 11, 12 Here we present evidence that Aurora B kinase activity directly promotes MCC production by working downstream of Mps1 in budding yeast and human cells. 3, 4, 5, 6, 7, 8 The error correction mechanism is regulated by the Aurora B kinase, but Aurora B also promotes SAC signaling via indirect mechanisms. 2 The SAC becomes active when Mps1 kinase sequentially phosphorylates the kinetochore protein Spc105/KNL1 and the signaling proteins that Spc105/KNL1 recruits to facilitate the production of the mitotic checkpoint complex (MCC). It is ensured by the combined activity of the spindle assembly checkpoint (SAC), 1 a signaling mechanism that delays anaphase onset in response to unattached chromosomes, and an error correction mechanism that eliminates syntelic attachments. Accurate chromosome segregation during cell division requires amphitelic chromosome attachment to the spindle apparatus.