title: Thrombotic microangiopathies and the linkage between von Willebrand factor and the alternative complement pathway.
abstract: Molecular linkages between von Willebrand factor (VWF) and the alternative complement pathway (AP) have recently been discovered. Endothelial cell (EC)-anchored ultra-large (UL) VWF multimeric strings function as an activating surface for the AP. C3 (in active C3b form) binds to the EC-anchored ULVWF strings, and promotes the assembly of C3bBb (C3 convertase) and C3bBbC3b (C5 convertase). These linkages may help to explain enigmatic clinical problems related to thrombotic microangiopathies, including some cases of refractory thrombotic thrombocytopenic purpura (TTP), TTP associated with only mild-modest deficiencies of ADAMTS-13, the provocation (or exacerbation) of acute episodes in patients with the atypical hemolytic uremic syndrome, and thrombosis in paroxysmal nocturnal hemoglobinuria. Recent experiments have also demonstrated that complement factor H performs a dual role: participating in regulation of the AP by binding to EC-anchored ULVWF strings; and functioning as a reductase to decrease the size of soluble VWF multimers.
authors: Department of Bioengineering, Rice University, Houston, Texas.
authors: Nancy
authors: N
authors: Turner
authors: Department of Bioengineering, Rice University, Houston, Texas.
authors: Leticia
authors: L
authors: Nolasco
authors: Department of Bioengineering, Rice University, Houston, Texas.
authors: Jennifer
authors: J
authors: Nolasco
authors: Department of Bioengineering, Rice University, Houston, Texas.
authors: Sarah
authors: S
authors: Sartain
authors: Department of Bioengineering, Rice University, Houston, Texas.
authors: Joel
authors: J
authors: Moake
mesh_terms: D065766:Atypical Hemolytic Uremic Syndrome / Q000503:physiopathology; D017242:Complement Factor H / Q000502:physiology; D015938:Complement Membrane Attack Complex / Q000502:physiology; D003170:Complement Pathway, Alternative / Q000502:physiology*; D006457:Hemoglobinuria, Paroxysmal / Q000503:physiopathology; D006801:Humans; D011697:Purpura, Thrombotic Thrombocytopenic / Q000503:physiopathology; D013927:Thrombosis / Q000503:physiopathology; D057049:Thrombotic Microangiopathies / Q000235:genetics / Q000503:physiopathology*; D014841:von Willebrand Factor / Q000502:physiology*
chemical_list: D015938:Complement Membrane Attack Complex; D014841:von Willebrand Factor; D017242:Complement Factor H