{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:53:21Z","timestamp":1787025201418,"version":"build-2736575974"},"reference-count":40,"publisher":"American Diabetes Association","issue":"6","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,6,1]]},"abstract":"<jats:p>Human diabetic neuropathy is multifactorial in etiology, with ischemia as a final common pathology. Although impaired vascular endothelial cell function in diabetic microvascular injury is established, the role of thrombomodulin (TM)-dependent protein C antithrombotic mechanism in the pathogenesis of neuropathy is unclear. This neuropathologic case-control study investigated whether vascular endothelial TM expression is deficient in peripheral nerve microvessels in diabetic neuropathy. Sural nerve biopsies from 7 patients with diabetic neuropathy and 10 with axonal neuropathy without vasculopathy were immunostained with anti-TM and anti\u2013von Willebrand factor (vWF; an endothelial cell marker) antibodies. The proportion of TM-positive microvessels was expressed relative to total vWF-staining vessels, according to vessel caliber and regional distribution within the nerve. In diabetic nerves compared with reference controls, the proportion of TM-positive endoneurial microvessels was 15-fold lower (0.02 vs. 0.30 in diabetic nerves vs. controls, P &amp;lt; 0.004), and the proportion of small-caliber epineurial microvessels was 10-fold lower (0.04 vs. 0.43, P &amp;lt; 0.001). No TM expression was detected at the perineurium in diabetic or control nerves. We demonstrate a substantial reduction of vascular endothelial TM expression throughout human diabetic neuropathy. These findings suggest that an impaired native TM-dependent protein C antithrombotic mechanism may contribute to microvascular ischemia in the pathogenesis of diabetic neuropathy.<\/jats:p>","DOI":"10.2337\/diabetes.51.6.1957","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T14:04:22Z","timestamp":1173189862000},"page":"1957-1963","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":24,"title":["Thrombomodulin Deficiency in Human Diabetic Nerve Microvasculature"],"prefix":"10.2337","volume":"51","author":[{"given":"Charlene E.","family":"Hafer-Macko","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland"},{"name":"Department of Gerontology, University of Maryland School of Medicine, Baltimore, Maryland"},{"name":"Baltimore Veterans Administration Medical Center - Geriatrics Research, Education, and Clinical Center, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick M.","family":"Ivey","sequence":"additional","affiliation":[{"name":"Department of Gerontology, University of Maryland School of Medicine, Baltimore, Maryland"},{"name":"Baltimore Veterans Administration Medical Center - Geriatrics Research, Education, and Clinical Center, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kymberly A.","family":"Gyure","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Sorkin","sequence":"additional","affiliation":[{"name":"Department of Gerontology, University of Maryland School of Medicine, Baltimore, Maryland"},{"name":"Baltimore Veterans Administration Medical Center - Geriatrics Research, Education, and Clinical Center, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard F.","family":"Macko","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland"},{"name":"Department of Gerontology, University of Maryland School of Medicine, Baltimore, Maryland"},{"name":"Baltimore Veterans Administration Medical Center - Geriatrics Research, Education, and Clinical Center, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031209393229200_R1","unstructured":"National Center for Health Statistics: Health, United States, 1998. 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