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Publications (5)7.55 Total impact

  • Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 12/2013; 41(12):1059-1060.
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    ABSTRACT: We previously reported the emerging role of OX40-OX40L interaction in inflammation and atherosclerosis. However, the mechanism by which OX40-OX40L interaction contributes to pathogenesis is poorly understood. This study investigated the effects of OX40-OX40L interaction on the nuclear factor of activated T cells c1 (NFATc1) in ApoE(-/-) mice. Atherosclerotic plaque was induced via rapid perivascular carotid collar placement in ApoE(-/-) mice. The expression levels of OX40, OX40L, and NFATc1 in the lymphocytes were measured via real-time polymerase chain reaction and flow cytometry. The presence of NFATc1 in the atherosclerotic plaque was detected via immunohistochemistry, and the level of IL-4 was measured via enzyme-linked immunosorbent assay. The expression level of NFATc1 significantly increased in atherosclerotic lesion and in the leukocytes from the ApoE(-/-) mice. After stimulating OX40-OX40L interaction, the mRNA and protein expression levels of NFATc1 in the lymphocytes significantly increased. Meanwhile, anti-OX40LmAb significantly suppressed the expression of NFATc1 in the leukocytes and substantially elevated the level of IL-4. NFATc1 inhibitor markedly suppressed IL-4 production. This study suggests that OX40-OX40L interaction regulates the expression of NFATc1, which may play a critical role in atherosclerotic plaque formation, and may therefore have implications with pathophysiology of atherosclerosis.
    Inflammation 09/2013; · 2.46 Impact Factor
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    ABSTRACT: To investigate the effect of OX40/OX40L interaction on the nuclear factor of activated T cells c1 (NFATc1) in ApoE-/- mice. Lymphocytes were prepared from mouse spleens after Collar-treated Surgery, then incubated with a range of agonistic anti-OX40 mAbs and inhibitory anti-OX40L mAb to stimulate or inhibit OX40-OX40L interaction in vitro. The expression of NFATc1 mRNA and protein in lymphocytes of ApoE-/- mice was measured by Real Time PCR and flow cytometry, respectively. (1) After stimulating OX40-OX40L signal pathway, the expression of NFATc1 mRNA and protein in leukocytes of ApoE-/- mice was significantly increased, with maximal effect occurring at 20 µg/ml anti-OX40 mAb-stimulated, and peaked at 24 h at any concentration (P < 0.01). (2) Anti-OX40L mAb significantly suppressed the expression of NFATc1 in leukocytes of ApoE-/- mice, with maximal effect occurring at 20 µg/ml anti-OX40L mAb, and peaked at 24 h (P < 0.001). OX40-OX40L interaction can regulate the mRNA and protein expressions of NFATc1 in lymphocytes of ApoE-/- mice.
    Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 06/2011; 39(6):526-30.
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    ABSTRACT: OBJECTIVE: Increasing evidence shows that OX40 ligand (OX40L, also known as tumor necrosis factor superfamily member 4, TNFSF4) system plays an important role in the pathogenesis of atherosclerosis. We investigate whether OX40L system (serum and monocytes OX40L levels) expression is disordered and the relationship with matrix metalloproteinases (MMPs) level and stability of coronary atherosclerotic plaque in patients with an acute coronary syndrome (ACS). METHODS: Thirty normal controls and 150 patients including 40 with stable angina (SA), 70 with unstable angina (UA), and 40 with acute myocardial infarction (AMI) were investigated. The expression of OX40L on monocytes was analyzed by flow cytometry, serum soluble OX40L and MMP-9, MMP-3 level was determined by ELISA. All coronary stenosis with >/=30% diameter reduction was assessed by angiographic coronary stenosis morphology. RESULTS: Patients with ACS showed a significant increase of OX40L (61.5+/-11.5 MFI) expression on monocytes compared with control (28.9+/-7.4 MFI) and SA group (31.2+/-8.1 MFI) (p<0.001). sOX40L also showed higher level in patients with ACS (34.6+/-9.3pg/ml) than in control (10.2+/-4.7pg/ml, p<0.001) and SA group (11.4+/-5.8pg/ml, p<0.001). Serum MMP-3 and MMP-9 in patients with ACS were 2 times greater than those in control. A positive correlation was found between MMP-9, MMP-3 and OX40L expression on monocytes as well as on sOX40L levels. A positive correlation was also observed between OX40L expression with sOX40L level and complex coronary stenosis (r(1)=0.61, r(2)=0.57, p<0.001). CONCLUSION: Patients with ACS show increased OX40L system expression which may create a proinflammatory and prothrombotic milieu for aggravating the development of atherosclerosis and instability of atherosclerotic plaques, and may be a valuable marker for predicting the severity of ACS.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 09/2008; · 2.24 Impact Factor
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    ABSTRACT: Increasing evidence show that OX40 ligand (OX40L), also known as tumor necrosis factor superfamily member 4 (TNFSF4), plays an important role in the pathogenesis of atherosclerosis. We investigated whether expression levels of soluble OX40L in serum and of membrane OX40L on platelets were related to serum concentrations of matrix metalloproteinases (MMPs) and stability of coronary atherosclerotic plaque in patients with acute coronary syndrome (ACS). We included healthy controls (n=30), patients with stable angina (SA) (n=40) and patients with ACS, including unstable angina (UA) (n=70) and acute myocardial infarction (AMI) (n=40). The expression of OX40L on platelets (pOX40L) was analyzed with flow cytometry whereas serum concentrations of soluble OX40L (sOX40L), MMP-9 and MMP-3 were determined with ELISA. All coronary stenoses with >or=30% diameter reduction were assessed by angiographic coronary stenosis morphology. The expression of OX40L on platelets were significantly higher in patients with ACS (61.5+/-11.5) compared with healthy controls (28.9+/-7.4) or with the group of patients with SA (31.2+/-8.1) (mean fluorescence intensity+/-SD) (p<0.001). Similarly, we observed higher sOX40L concentrations in patients with ACS (34.6+/-9.3) compared with controls (10.2+/-4.7) or patients with SA (11.4+/-5.8) (ng/ml+/-SD) (p<0.001). Serum MMP-3 and MMP-9 levels in patients were two times greater than those in the control group. A positive correlation was observed between OX40L expression on platelets and MMP-9 and MMP-3 serum concentrations. OX40L expression on platelets were furthermore correlated with soluble OX40L in serum and with complex coronary stenoses (r1=0.61, r2=0.57, p<0.001). Patients with ACS show increased OX40L system (pOX40L and sOX40L) expression which may create a proinflammatory milieu for aggravating the development of atherosclerosis, and may be a valuable marker for predicting the severity of ACS.
    Clinica Chimica Acta 07/2008; 397(1-2):22-6. · 2.85 Impact Factor