McCarron R M, Doron D A, Sirén A L, Feuerstein G, Heldman E, Pollard H B, Spatz M, Hallenbeck J M
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Brain Res. 1994 Jun 6;647(2):265-72. doi: 10.1016/0006-8993(94)91326-9.
Lipopolysaccharide (LPS)-induced (i.v. or i.c.v., 1.8 mg/kg) release of von Willebrand factor (vWF) was examined in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. SHR rats released significantly (P < 0.05) more vWF than WKY rats in response to LPS. LPS also inhibited factor VIII procoagulant activity (FVIII:c) which may indicate an increase in thrombin activity. Cultured cerebrovascular endothelial cells (EC) derived from both SHR and WKY rats, as well as human umbilical vein EC (HUVEC) cultures constitutively released vWF. Treatment with agonists including LPS, thrombin and tumor necrosis factor-alpha (TNF alpha) did not affect the in vitro secretion of vWF by cerebrovascular EC cultures but significantly upregulated vWF release by HUVEC cultures. Preincubation of cerebrovascular EC cultures with interleukin-1 (IL-1) +/- TNF alpha or co-culturing in the presence of LPS-activated syngeneic monocytes had no effect on vWF secretion. The findings demonstrate that conditions of hypertension may affect endothelial cells and make them more responsive to agonist stimulation and thereby increase secretion of vWF, an important factor in hemostasis as well as thrombosis. The capacity of LPS to significantly affect the in vivo secretion of vWF in SHR and WKY rats but not cultured cerebrovascular EC indicates that observed elevations in plasma vWF were not derived from cerebrovascular EC. It is suggested that hypertension may function as a risk factor for thrombotic stroke by influencing factors involved in coagulation processes, such as vWF and factor VIII:c.
在自发性高血压大鼠（SHR）和血压正常的Wistar-Kyoto（WKY）大鼠中，检测了脂多糖（LPS）诱导（静脉注射或脑室内注射，1.8mg/kg）的血管性血友病因子（vWF）释放情况。与WKY大鼠相比，SHR大鼠对LPS的反应显著（P<0.05）释放更多的vWF。LPS还抑制了凝血因子VIII促凝活性（FVIII:c），这可能表明凝血酶活性增加。源自SHR和WKY大鼠的培养脑血管内皮细胞（EC）以及人脐静脉EC（HUVEC）培养物可组成性释放vWF。用包括LPS、凝血酶和肿瘤坏死因子-α（TNFα）在内的激动剂处理，并不影响脑血管EC培养物中vWF的体外分泌，但显著上调了HUVEC培养物中vWF的释放。用白细胞介素-1（IL-1）+/-TNFα预孵育脑血管EC培养物，或在LPS激活的同基因单核细胞存在下共培养，对vWF分泌没有影响。这些发现表明，高血压状态可能影响内皮细胞，使其对激动剂刺激更敏感，从而增加vWF的分泌，vWF是止血和血栓形成中的一个重要因素。LPS显著影响SHR和WKY大鼠体内vWF分泌，但不影响培养的脑血管EC，这表明观察到的血浆vWF升高并非源自脑血管EC。提示高血压可能通过影响凝血过程中涉及的因素，如vWF和FVIII:c，而成为血栓性中风的一个危险因素。
