Clinical significance of costimulatory molecules CD40/CD40L and CD134/CD134L in coronary heart disease

Abstract

The aim of the study was to evaluate the potential role of CD40/CD40 ligand (CD40L) and CD134/CD134 ligand (CD134L) in the development of coronary heart disease (CHD) via the performance of a case-control study.The research objects were 234 cases of CHD patients and 120 cases of well-matched normal controls. Following the separation of peripheral blood mononuclear cells (PBMCs), real-time quantitative PCR (qRT-PCR), Western blot, immunohistochemistry, and flow cytometry were applied for the detection of mRNA levels and expression levels of CD40/CD40L and CD134/CD134L; meanwhile, intercellular adhesion molecule-1 (ICAM-1) and Fas protein mRNA levels were detected using qRT-PCR.There was no statistical difference in the comparison of baseline characteristics between groups, indicating comparability between groups. qRT-PCR and Western blot analysis indicated that CD40/CD40L and CD134/CD134L mRNA and protein expression levels were all increased in the CHD group than those in the control group. Flow cytometry further confirmed the similar tendency. Meanwhile, ICAM-1 and Fas protein mRNA levels were elevated in the CHD group and positively correlated with the above parameters. Furthermore, CD40/CD40L expression rates were negatively correlated with gender and different types of CHD. Meanwhile, CD134/CD134L expressions were also higher in male patients, in patients with family history, previous history of hypertension, diabetes, and cerebrovascular diseases.CD40/CD40L and CD134/CD134L are increased and may have potential correlation with clinical pathological features of patients with CHD. Further in-depth exploration of costimulatory molecules for CHD guidance as well as intrinsic mechanisms are needed combined with in vivo and in vitro experiments.

Identification of Four Potential Biomarkers Associated With Coronary Artery Disease in Non-diabetic Patients by Gene Co-expression Network Analysis

“…The possible mechanisms by which the CD40 and CD40L systems affected atherosclerosis might be correlated with the immune inflammatory reaction (Gocmen et al, 2011;Fu et al, 2013;Hashem et al, 2014). Consistent with the results of the study by Chen et al (2017), we also found that both CD40 mRNA and protein expression levels were increased in the patients with luminal stenosis of ≥50% in ≥1 major vessel compared with the control group, though the level of CD40 was downregulated through bioinformatics analysis. The current discrepancy may result from the following possibilities.…”

Functional crosstalk between T cells and monocytes in cancer and atherosclerosis

“…Furthermore, global OX40L overexpression and deletion increases and reduces fatty streak formation, respectively, in high‐fat diet‐fed mice 145,146 . Plaque‐resident CD4 + T cells and Mϕs express OX40 and OX40L, respectively, 145 and accumulation of TNFRSF4 and TNFSF4 transcripts, which encode OX40 and OX40L, correlate with CVD risk 159 . While there have been no clinical trials on these targets to date, an anti‐OX40 antagonistic Ab that elicits increased OX40 + T cells is currently under trial for individuals with solid tumors 160 …”

Analysis of Genetic Variation in CD40 and CD40L: Relationship with mRNA Relative Expression and Soluble Proteins in Acute Coronary Syndrome

“…Other studies analyzed CD40 / CD40L mRNA expression levels in coronary artery disease (CHD), following the separation of peripheral blood mononuclear cells and qRT-PCR, and found significantly increased expression levels of both genes in the CHD group compared to the control group [24].…”