Effects of rosiglitazone on the synthesis of tumor necrosis factor-alpha and tissue factor in peripheral blood monouclear cells from patients with acute coronary syndrome without diabetes

Abstract

Abstract: AIM: To study the effects of rosiglitazone on the synthesis of tumor necrosis factor-alpha (TNF-α), tissue factor (TF), and tissue factor activity (TFA) in peripheral bloodmonouclear cells(PBMC) from patients with acute coronary syndrome (ACS) without diabetes.METHODS: The PBMC from patients with ACS without diabetes were isolated and incubated with rosiglitazone (0.0, 0.1, 1.0, 10.0 μmol/L, respectively) for 24 hours.The concentrations of TNF-αin culture medium and the levels of mononuclear cell tissue factor (MCTF) were measured by using enzyme-linked immunosorbent assay (ELISA), and the mRNA expressions in monocytes were detected by reverse- transcriptase polymerase chain reaction (RTPCR), and TF activity was determined by chromogenic substrate assay.RESULTS: Rosiglitazone(0.0, 0.1, 1.0, 10.0 μmol/L) dose-dependently suppressed the synthesis of TNF-α, TF, and TFA in PBMC from patients with ACS without diabetes.In correspondence with the concentrations of 0.0 、0.1 、1.0 、10.0 μmol/L rosiglitazone, the levels of TNF-αprotein were respectively (306 ±40), (262 ±32), (236 ±28), (194 ± 23) ng/L, the ratios of relative semi-quantitative absorption value of TNF-αmRNA expression were respectively (0.78 ±0.14), (0.60 ±0.09), (0.39 ± 0.11), (0.30 ±0.11), the antigens levels of synthesis of TF were respectively (5.8 ±1.3), (4.6 ±0.9), (3.3 ±0.5), (3.0 ±0.3) ng/L, the ratios of relative semi-quantitative absorption value of TF mRNA expression were respectively (0.42 ± 0.11), (0.37 ± 0.10), (0.31 ±0.09), (0.22 ±0.08) and the expressions of TFA were (16.2 ±3.2), (8.6 ±2.0), (5.4 ±0.6), (4.4 ±0.8) pmol/L (all P <0.05). CONCLUSION: Our findings show that rosiglitazone reduces the synthesis of TNF-α, TF, and TFA in PBMC from patients with ACS without diabetes, that indicates rosiglitazone has the antiinflammatory and antithrombotic effects on ACS besides reducing blood glucose, and it might play a potential and important role in prevention and therapy in ACS.

Key words: rosiglitazone, acute coronary syndrome, tumour necrosis factor-alpha, tissue factor

CLC Number:

WU Xu-bin, QIAN Zong-jie, WU Guang-wei, LIN Ying-zhong, HU Chang-xin. Effects of rosiglitazone on the synthesis of tumor necrosis factor-alpha and tissue factor in peripheral blood monouclear cells from patients with acute coronary syndrome without diabetes[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(2): 180-185.

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