Oral fibrinogen-depleting agent lumbrokinase for secondary ischemic stroke prevention: results from a multicenter, randomized, parallel-group and controlled clinical trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Elevated fibrinogen (Fg) level is a known risk factor for ischemic stroke. There are few clinical trials on oral fibrinogen-depleting therapies for secondary ischemic stroke prevention. We aimed to assess the effects of one-year therapy with oral lumbrokinase enteric-coated capsules on secondary ischemic stroke prevention.</p><p><b>METHODS</b>This is a multicenter, randomized, parallel group and controlled study that began treatment in hospitalized patients with ischemic stroke and continued for 12 months. Patients were randomized to either the control group that received the standard stroke treatment or the fibrinogen-depleting group that received the standard stroke treatment plus enteric-coated lumbrokinase capsules. The NIH Stroke Scale scores (NIHSSs) and plasma Fg level were recorded. The carotid artery intima-media thickness (IMT) and status of plaques were examined through carotid ultrasound examination. Primary outcomes included all-cause mortality, any event of recurrent ischemic stroke/transient ischemic attack (TIA), hemorrhagic stroke, myocardial infarction and angina, and other noncerebral ischemia or hemorrhage. Kaplan-Meier survival analysis and the Long-rank test were used to compare total vascular end point incidence between the two groups. Comparison of median values between two groups was done by the Student t test, one-way analysis of variance (ANOVA), or non-parametric rank sum test.</p><p><b>RESULTS</b>A total of 310 patients were enrolled, 192 patients in the treatment group and 118 patients in the control group. Compared to the control group, the treatment group showed favorable outcomes in the Fg level, carotid IMT, the detection rate of vulnerable plaques, the volume of carotid plaques, NIHSS scores, and incidence of total vascular (6.78% and 2.08%, respectively) and cerebral vascular events (5.93% and 1.04%, respectively) (P < 0.05). In the treatment group, the volume of carotid plaques was significantly related to the carotid IMT, the plaque diameter, width and number (P = 0.000, 0.000, 0.000, 0.022; F = 13.51, 2.52, 11.33, -3.29, but there was a weak correlation with the Fg level (P = 0.056). After 1-year therapy, the incidence of overall vascular end points was reduced by 4.7%.</p><p><b>CONCLUSION</b>Long-term oral fibrinogen-depleting therapy may be beneficial for secondary ischemic stroke prevention.</p>

Effect of fibrinogen, fibrin and fibrin (ogen) degradation products on the tissue plasminogen activator and plasminogen activator inhibitor-1 expressions of vascular endothelial cells in coculture system / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of fibrinogen (Fg), fibrin (Fb) and fibrin (ogen) degradation products (FDPs) on tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) expressions of human umbilical vein endothelial cells (HUVECs) in coculture system.</p><p><b>METHODS</b>Fg, Fb and FDPs at various concentrations (0, 0.5, 1.5, 3.0, 4.5 and 6.0 g/L) were added to the transwell coculture system of HUVECs and smooth muscle cells (SMCs) for 24 hours. The expressions of tPA and PAI-1 at mRNA level were examined by RT-PCR and tPA and PAI-1 protein and activity were detected by ELISA and substrate chromogenic assays.</p><p><b>RESULTS</b>tPA expression was not affected by Fg. Fg at concentrations between 3.0 - 4.5 g/L significantly enhanced the mRNA expression, protein content and activity of PAI-1, while expression of PAI-1 was significantly inhibited by Fg at concentration of 6.0 g/L. Fb at concentrations between 3.0 - 4.5 g/L significantly up-regulated mRNA expression, increased protein content and down-regulated activity of tPA. Fb (1.5 - 4.5 g/L) also enhanced the mRNA expression, increased protein content and activity of PAI-1. FDPs at concentrations 3.0 - 6.0 g/L down-regulated the expression of tPA and FDPs at concentrations 1.5 - 6.0 g/L significantly enhanced PAI-1 mRNA expression.</p><p><b>CONCLUSION</b>Fg, Fb and FDPs play important roles in the pathogenesis of atherosclerosis by modulating the expression of tPA and PAI-1 of endothelial and SMCs.</p>

Establishment of the coculture systems of rabbit aortic endothelial cells and smooth muscle cells / 中国应用生理学杂志

<p><b>AIM</b>In order to establish a coculture system of ECs and SMCs and by which further study can be done.</p><p><b>METHODS</b>ECs in primary culture were grown on a side of Transwell membrane, and SMCs were grown on an other side of it or the bottom of culture well, so that two kinds of coculture systems were established, and detail observation on the coculture systems was carried out by transmission and scanning electron microscope.</p><p><b>RESULTS</b>ECs in primary culture were positive of VI factor by immunocytochemistry staining. ECs and SMCs were grown well on both sides of Transwell membrane, relative to ECs monolayer of "cobblestone appearance", SMCs were multilayer of "hills and valleys appearance". ECs and SMCs on both sides of Transwell membrane could form the gap junctions by micropores.</p><p><b>CONCLUSION</b>The coculture systems of ECs and SMCs were established successfully by modeling the structural relationship of vascular wall.</p>