Related Experiment Video
Updated: Aug 11, 2026
A Semi-Automated and Reproducible Biological-Based Method to Quantify Calcium Deposition In Vitro
Published on: June 2, 2022
CD40-CD154 expression in calcified and non-calcified coronary lesions of patients with chronic renal failure
Valentina Campean1, Daniel Neureiter, Barbara Nonnast-Daniel
1Department of Pathology, University of Erlangen-Nürnberg, Germany.
Insights
Patients with chronic renal failure (CRF) exhibit accelerated atherosclerosis, particularly calcified lesions. This study reveals heightened inflammation and CD40-CD154 pathway involvement in CRF coronary plaques, suggesting a key role in cardiovascular complications.
Area of Science:
- Cardiovascular pathology
- Nephrology
- Immunology
Background:
- Patients with chronic renal failure (CRF) experience a higher incidence of cardiovascular complications, often linked to accelerated atherosclerosis.
- The precise mechanisms driving this accelerated atherosclerosis in CRF remain incompletely understood, with chronic micro-inflammation being a potential contributor.
- The CD40-CD154 interaction is crucial for cell activation and adhesion molecule regulation in atherosclerosis.
Purpose of the Study:
- To investigate the expression and distribution of CD40 and its ligand (CD154) in coronary atherosclerotic lesions of patients with and without CRF.
- To analyze the correlation between CD40-CD154 expression, inflammatory markers (CRP), and the presence and type of calcification in coronary plaques.
- To compare the inflammatory status and CD40-CD154 signaling pathway activity between CRF and non-renal control patients.
Main Methods:
- Coronary plaques from 57 patients (with and without CRF) were classified using the Stary classification.
- Immunohistochemistry and a semiquantitative scoring system were employed to assess in situ protein expression of CD40, CD154, and C-reactive protein (CRP).
- Analysis included cell infiltration patterns and correlation with lesion type and calcification.
Main Results:
- CD40 was overexpressed in medial myocytes and present on endothelial cells, T lymphocytes, macrophages, fibroblasts, and smooth muscle cells within plaques.
- CD154 expression was observed on T cells in areas with CD40-positive macrophages.
- Both uremic and control patients showed higher CD40, CD154, and CRP expression in calcified lesions compared to non-calcified ones.
- CRF patients exhibited distinct CD40 and CD154 expression patterns and significantly higher CRP levels in coronary plaques than controls.
Conclusions:
- Coronary atherosclerotic lesions in CRF patients demonstrate an elevated inflammatory status.
- The CD40-CD154 signaling pathway is implicated in the pathogenesis of atherosclerosis in CRF patients.
- These findings highlight the CD40-CD154 pathway's particular relevance in calcified atherosclerotic lesions within the context of chronic renal failure.
Abstract:
The high incidence of cardiovascular complications in patients with chronic renal failure (CRF) is partly explained by more aggressive atherosclerosis, i.e. increased incidence and severity of lesions with higher tendency to calcification. The pathogenesis of this accelerated atherosclerosis, however, is not completely understood. Among other risk factors, chronic micro-inflammation may be involved. Activation of cells and adhesion molecules in atherosclerosis is governed by CD40-CD154 (CD40 ligand) interaction. Therefore, we investigated the expression and distribution of CD40-CD154 in different coronary atherosclerotic lesions of CRF patients and non-renal control patients. Coronary plaques of 57 patients with and without CRF were categorized according to the Stary classification and analysed for in situ protein expression of CD40, CD154 and CRP using immunohistochemistry and a semiquantitative scoring system. The nature, number and distribution of infiltrating cells was analysed and correlated to the types of coronary lesions and in particular to the presence of calcification. CD40 was over expressed in media myocytes of coronary plaques of both uremic and control patients. Inside the plaques, CD40 was expressed on endothelial cells, T lymphocytes, macrophages, fibroblasts, and smooth muscle cells. CD154 expression was seen on T cells in areas densely infiltrated by CD40 positive macrophages. In uremic and control patients higher in situ expression of CD40, CD154 and CRP was seen in calcified compared to non-calcified lesions. Inside the plaques, there were significant differences in the expression pattern of CD40 and CD154 between uremic and control patients. In addition, in uremic patients coronary plaques showed higher CRP protein expression compared to control patients. The data indicate a higher inflammatory status of coronary lesions as well as involvement of the CD40-CD154 signaling cascade in CRF patients, especially in cases of calcified atherosclerotic lesions.
