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Effects of Physiological Testosterone on Tissue Factor Pathway Inhibitor Expression by Cultured Endothelial Cells in Response to Inflammatory Mediators

Author: QiuWenBing
Tutor: WangDongMing
School: Shantou University
Course: Internal Medicine
Keywords: Testosterone Tumor necrosis factor -alpha Nuclear factor-kappaB Tissue factor pathway inhibitor Human umbilical vein endothelial cells
CLC: R541.4
Type: Master's thesis
Year: 2008
Downloads: 46
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Abstract

Background with acute coronary syndrome (ACS) is the critical illness of atherosclerotic coronary heart disease (CHD), although its incidence exist significant gender differences, but the role of androgen in patients with coronary heart disease has been controversial, is currently cardiovascular research in the field of one of the hot spots; research confirmed the anticoagulant activity of vascular endothelial reduce thrombosis is the main feature of the acute coronary syndrome. Our preliminary experiments found that physiological concentrations of testosterone (Testosterone, T) can promote human umbilical vein endothelial cells (HUVEC) the important anticoagulant tissue factor pathway inhibitor (TFPI) expression, and can be adjusted to include the nuclear factor-kappaB (NF-κB) including a plurality of activity of transcription factors. NF-κB is important mediators of the inflammatory process, activation-induced expression of inflammatory cytokines play an important role in the development of atherosclerosis. The study found that proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) can be adjusted the coagulation initiation factor - including tissue factor (TF) thrombosis factor activity, and some of the factors regulating NF-κB activation pathway, shows that testosterone and TNF-α on NF-κB activity of regulation, testosterone can interfere with TNF-α induced inflammatory state, however, to promote endothelial cell inflammatory state anticoagulant anticoagulant TFPI expression activity and its regulation whether through nuclear transcription factor NF-κB pathway has not been reported, the experiments that explore the above issues. Purpose by in vitro cultured human umbilical vein endothelial cells were observed physiological concentrations of testosterone, TFPI expression and NF-κB activity changes in TNF-α treatment, and to explore the physiological concentration of testosterone on the regulation of expression of endothelial cells in TNF-α-mediated inflammatory state TFPI and its mechanism. Method (1) 3-4 generations of in vitro cultured human umbilical vein endothelial cells (HUVEC) were divided into groups (cell groups), the simple medium control group, physiological concentrations of testosterone (30nmol / L) group, TNF-α ( 10ng/mL) group, TNF-α (20ng/mL) groups, respectively, and the latter two groups together with testosterone for 48h with MTT assay cell activity; (2) of HUVEC 3-4 generation is divided into a pure media control group, physiological concentrations of testosterone (30nmol / L) group, TNF-α (20ng/mL) group, and the two together group, culture the total TFPI protein content in the supernatant was detected by ELISA after 48h groups, real-time RT- PCR assay groups TFPI mRNA expression; (3) physiological concentrations of testosterone (30nmol / L), TNF-α (20ng/mL) respectively intervention as well as together in HUVEC 12h, the changes in the electrophoretic mobility assay (EMSA) technology to detect NF-κB activity changes. Results (1) testosterone and the concentration of TNF-α, respectively, role or common intervention 48 hours no significant impact on human umbilical vein endothelial cell activity; (2) TNF-α (20ng/mL) can significantly cut TFPI mRNA and protein levels (P lt; 0.001), physiological concentrations of testosterone (30nmol / L) to reduce the expression of TNF-α on TFPI inhibition (P lt; 0.05); (3) TNF-α (20ng/mL) can significantly activate NF-κB ( P lt; 0.05), physiological concentrations of testosterone (30nmol / L) not only can be used alone to inhibit NF-κB activity and can weaken the role of TNF-α on NF-κB activation (P lt; 0.05). Conclusion human umbilical vein endothelial cells, the proinflammatory cytokines TNF-α can inhibit the expression of TFPI; physiological concentrations of testosterone can weaken the expression of TNF-α on TFPI inhibition, and thus play a role in preventing thrombosis in the inflammatory state; while The mechanism of action may be achieved through the inhibition of NF-κB activation.

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Coronary arteries ( atherosclerosis ),heart disease (CHD)
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