title: Associations of plasma von Willebrand factor ristocetin cofactor activity and 5-hydroxyindole acetic acid concentrations with blood flow in lower-leg arteries in Japanese type 2 diabetic patients with normal ankle-brachial index.
abstract: OBJECTIVE
  To evaluate the associations of circulating levels of proinflammatory molecules and endothelial factors with blood flow in lower-leg arteries in diabetic patients with normal ankle-brachial index (ABI>0.9).
  
  
  METHODS
  We enrolled 123 type 2 diabetic patients with normal ABI and 30 age-matched nondiabetic subjects consecutively admitted to our hospital. Flow volume and resistive index, an index of peripheral vascular resistance, at the popliteal artery were evaluated using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging. An automatic device was used to measure ABI and brachial-ankle pulse-wave velocity (baPWV) for evaluation of arterial stiffness. Plasma soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1) concentrations, serum high-sensitivity C-reactive protein (hsCRP) levels, plasma von Willebrand factor ristocetin cofactor activity (VWF), and plasma vasoconstrictor serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA) concentrations were measured.
  
  
  RESULTS
  Diabetic patients had higher baPWV (P<.0001), resistive index (P<.0001), sICAM-1 (P<.0001), MCP-1 (P=.0224), log hsCRP (P<.0001), VWF (P<.0001), 5-HIAA (P=.0015), and lower blood flow (P<.0001) than nondiabetic subjects. VWF (P=.0019) or 5-HIAA (P=.0011), but not sICAM-1, MCP-1, and log hsCRP, was negatively correlated with blood flow in diabetic patients. A multivariate analysis revealed that the significant independent determinants of blood flow were hypertension, use of renin-angiotensin system inhibitors, VWF and 5-HIAA (r(2)=0.198, P<.0001) in diabetic patients.
  
  
  CONCLUSIONS
  Plasma VWF and 5-HIAA concentrations are associated with blood flow and are involved in the pathogenesis of impaired peripheral circulation due to higher arterial stiffness and greater vascular resistance in lower-leg arteries in diabetic patients with normal ABI.
authors.affiliation: Department of Internal Medicine, Daiyukai General Hospital, 1-9-9 Sakura, Ichinomiya, Aichi 491-8551, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murase
authors.forename: Eiji
authors.initials: E
authors.lastname: Suzuki
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tajima
authors.forename: Kanako
authors.initials: K
authors.lastname: Hayashi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Nakamura
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Noritake
authors.forename: Jun
authors.initials: J
authors.lastname: Takeda
mesh_terms: D000368:Aged; D055109:Ankle Brachial Index; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D044466:Asian People; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood*; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007866:Leg / Q000098:blood supply* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012310:Ristocetin / Q000097:blood*; D014655:Vascular Resistance; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D000959:Antihypertensive Agents; D016207:Cytokines; D007004:Hypoglycemic Agents; D014841:von Willebrand Factor; D012310:Ristocetin; D006897:Hydroxyindoleacetic Acid