title: Local variation in expression of pro- and antithrombotic factors in vascular endothelium of human autopsy brain.
abstract: The expression of tissue factor (TF), tissue factor pathway inhibitor (TFPI), von Willebrand factor (vWF), endothelial nitric oxide (NO) synthase (eNOS), tissue plasminogen activator (tPA), its inhibitor (PAI-1), and myosin, an indicator of local shear stress, was examined in the endothelium of cerebral vessels according to vessel size and location in human autopsy brains, using immunohistochemistry. Expression of TF, vWF, eNOS, tPA/PAI-1, and myosin was much greater in intracerebral perforating arteries and the microvasculature than the pial and carotid arteries. Expression of all antigens studied was normally faint or negative in the pial and carotid arteries. However, TF, vWF, myosin, tPA, and PAI-1 were strongly expressed in the endothelium of the inner wall of the carotid bifurcation where flowing blood collides, but not in the outer wall. In the endothelium of arteries with fibrillary hyperplasia, vWF, myosin, eNOS, tPA, and PAI-1 were strongly expressed. Within the brain, microvascular expression of TFPI was very faint or negative, whereas that of vWF was intense throughout all brain regions. However, expression of TF and myosin was more intense in the basal gray matter and white matter than in the cortex. eNOS was expressed more strongly in the basal gray matter and cortex than the white matter, whereas tPA and PAI-1 expression was more intense in the white matter than the gray matter. In addition to intrinsic properties of individual vessels, these local variations in expression of pro- and antithrombotic factors in cerebral vessels may in part be due to differences in hemorheological and humoral environments to which they are exposed, and may result in local difference in vulnerability to ischemia. The present findings may in part account for the propensity of thrombus generation in the carotid inner wall, an usual source of artery-to-artery microemboli, frequent development of lacunar (small) infarcts in deep brain regions, and diffuse white matter lesions as seen in Binswanger's leukoencephalopathy.
authors.affiliation: Department of Neurology, Iwate Medical University, Morioka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tohgi
authors.forename: K
authors.initials: K
authors.lastname: Utsugisawa
authors.forename: M
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Y
authors.initials: Y
authors.lastname: Nagane
authors.forename: M
authors.initials: M
authors.lastname: Ukitsu
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000378:metabolism*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D002102:Cadaver; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D009218:Myosins / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; C051928:lipoprotein-associated coagulation inhibitor; D014841:von Willebrand Factor; D013925:Thromboplastin; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D010959:Tissue Plasminogen Activator; D009218:Myosins