The CD40-CD40L system in cardiovascular disease

Pamukçu, Burak; Lip, Gregory Y.H.; Snezhitskiy, V. A.; Shantsila, Eduard

doi:10.3109/07853890.2010.546362

Cited by 117 publications

(94 citation statements)

References 88 publications

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“…They are gaining increasing attention in the field of tumor immunology (6)(7)(8). It has been reported that CD40-CD40L axis was involved in a series of cell biological activities, such as cancer, cardiovascular disease, immune disorders, and even Alzheimer's disease (9)(10)(11). CD40 was found to be expressed at an up-regulated level in many epithelial cancers (12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Expression of the co-signaling molecules CD40-CD40L and their growth inhibitory effect on pancreatic cancer in vitro

Zhao

Fei

et al. 2012

Oncol Rep

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Abstract. We investigated the expression of the co-signalling molecule CD40 in pancreatic cancer and the growth inhibitory effect of the recombinant soluble human CD40 ligand (rshCD40L) in pancreatic cancer cell lines. Twenty-six cases of pancreatic cancer tissues and corresponding paratumoral normal tissues were immunohistochemically analyzed for CD40 expression. The association of CD40 expression with clinicopathological parameters, including clinical stage, pathological grade, invasion and metastasis, were statistically analyzed. The serum sCD40 levels in pancreatic cancer patients were examined by ELISA. The expression of CD40 in the pancreatic cancer cell lines Panc-1, Aspc-1 and Miapaca-2 was examined by RT-PCR and flow cytometry. The growth inhibitory activity of rshCD40L on pancreatic cancer cell lines was determined by MTT assay. Tumor cell apoptosis was detected by TUNEL and Annexin V/ PI double staining method. CD40 was positive both on the membrane and in the cytoplasm of tumor cells, 69.2% (18/26) of the cases were positive for CD40. CD40 expression was significantly higher in pancreatic cancer tissues compared to adjacent normal tissues (P<0.05). High CD40 expression was associated with TNM stage and lymph node metastasis (both P<0.05). Patients with pancreatic cancer have higher serum sCD40L levels (3.53±0.70 ng/ml) compared to healthy subjects (1.81±0.48 ng/ml, P<0.05). rshCD40L significantly inhibited the proliferation of the pancreatic cancer cell lines and induced apoptosis in these cell lines. The co-signaling molecule CD40 is highly expressed in pancreatic cancer tissues and cell lines and rshCD40L is a potential tool for antitumor therapies.

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Section: Introductionmentioning

confidence: 99%

Expression of the co-signaling molecules CD40-CD40L and their growth inhibitory effect on pancreatic cancer in vitro

Zhao

Fei

et al. 2012

Oncol Rep

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“…The polymorphism H6D in GDF15 has not previously been shown to be important for CVD events, but serum levels of GDF15 were related to CVD in the general population 27,28 and in patients with RA 30 . Both CD40 and GDF15/MIC-1 have immunoregulatory properties 25,31,38 . In the patients with RA, we were able to confirm associations with these selected SNP and CVD.…”

Section: Rheumatologymentioning

confidence: 99%

Polymorphisms of the Genes EncodingCD40and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease

Ärlestig¹,

Rantapää-Dahlqvist²

2012

J Rheumatol

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Objective.Genes or gene products associated with coronary artery disease in the general population were analyzed in rheumatoid arthritis (RA) patients with atherothrombotic manifestations (ATM).Methods.A cross-sectional study of 681 individuals (498 women; 183 men) with RA (American College of Rheumatology criteria), a mean age of 60.6 ± 13.2 years, and mean disease duration of 15.5 ± 12.6 years who were consecutively recruited and followed for 6 years. The prevalence of ATM [i.e., myocardial infarction, angina pectoris with intervention, deep vein thrombosis/pulmonary embolism (DVT/PE), and/or stroke/transient ischemic attack (TIA)] was recorded. Polymorphisms were analyzed in the genes coding for growth differentiation factor 15 (GDF15)/monocyte inhibitory cytokine-1 (MIC-1; rs1058587),CD40(rs1535045 and rs3765459), and the 9p21.3 locus (rs1333049). Controls were randomly selected (n = 687; matched for age and sex).Results.The distribution of genotypes ofGDF15/MIC-1differed significantly between patients with RA and controls (chi-squared = 6.40, 2 df, p = 0.041). ATM were associated with polymorphism of theGDF15/MIC-1G allele (OR 2.21, 95% CI 1.17–4.18), and with CC genotype of the 9p21.3 locus (rs1333049; OR 1.92, 95% CI 1.15–3.19). Stroke/TIA in women was associated withGDF15/MIC-1GG genotype (OR 3.75, 95% CI 1.06–13.33), while stroke/TIA in men was associated withCD40homozygous major alleles (OR 6.48, 95% CI 1.31–32.0 and OR 2.78, 95% CI 0.78–9.91, respectively). DVT/PE was associated with polymorphism in theGDF15/MIC-1gene (rs1058587) minor allele (OR 3.53, 95% CI 1.30–9.58).Conclusion.The gene polymorphisms analyzed were associated with different ATM in RA. TheGDF15/MIC-1gene polymorphism was also associated with RAper se, suggesting a common etiology for RA and ATM.

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“…74 Most circulating CD40L is expressed in platelets, which are not only critical elements for homeostasis, but also have the potential to trigger an inflammatory response in the vascular wall. 75 Once activated, platelets promptly express CD40L, which, in turn, induces endothelial cells to secrete chemokines and to express adhesion molecules, thereby promoting the recruitment and extravasation of leukocytes at the site of injury.…”

Section: Cd40 Ligand (Cd40l)mentioning

confidence: 99%