title: Microvascular tissue plasminogen activator is reduced in diabetic neuropathy.
abstract: BACKGROUND
  Abnormalities of endogenous fibrinolysis are linked to diabetic macrovascular disease; whether key vascular endothelial regulatory proteins, such as tissue plasminogen activator (tPA), are altered in diabetic neuropathy microvasculature is unknown. This neuropathologic case: control study investigates the hypothesis that tPA expression is regionally deficient in microvessels in human diabetic neuropathy.
  
  
  METHODS
  tPA and von Willebrand factor (vWF), a vascular endothelial cell marker, are detected on vascular endothelium by immunoperoxidase methods with specific antibodies on formalin fixed paraffin embedded sural nerve biopsies from six diabetic and six axonal neuropathy control nerves without vasculopathy. The proportion of microvessels in each nerve region expressing tPA is determined by the ratio of tPA positive vessels/total vWF positive vessels on serial sections.
  
  
  RESULTS
  tPA expression is lower in diabetic neuropathy cases compared to controls in all regions, including epineurial (62.4 +/- 8.6% vs 91.0 +/- 1.6%, p < 0.02) and endoneurial microvessels (51.7 +/- 7.1% vs 91.5 +/- 2.9%, p < 0.001).
  
  
  CONCLUSIONS
  These results demonstrate a four- to sixfold increase in the number of peripheral nerve microvessels lacking immunodetectable tissue plasminogen activator in the epineurial and endoneurial vessels in diabetes, suggesting that impaired endogenous fibrinolysis might contribute to microvascular ischemia in human diabetic neuropathy.
authors.affiliation: Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201-1595, USA. cmacko@grecc.umaryland.edu
authors.forename: Charlene E
authors.initials: CE
authors.lastname: Hafer-Macko
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Ivey
authors.forename: John D
authors.initials: JD
authors.lastname: Sorkin
authors.forename: Richard F
authors.initials: RF
authors.lastname: Macko
mesh_terms: D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology; D003929:Diabetic Neuropathies / Q000201:enzymology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000201:enzymology; D006801:Humans; D008833:Microcirculation / Q000201:enzymology / Q000503:physiopathology; D013497:Sural Nerve / Q000098:blood supply* / Q000201:enzymology* / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism*
chemical_list: D010959:Tissue Plasminogen Activator