Microvascular tissue plasminogen activator is reduced in diabetic neuropathy.
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.
Hafer-Macko
Charlene E
CE
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201-1595, USA. cmacko@grecc.umaryland.edu
Ivey
Frederick M
FM
Sorkin
John D
JD
Macko
Richard F
RF
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*
D010959:Tissue Plasminogen Activator