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Published on: January 28, 2020
Inverse correlation between soluble CD40 ligand and soluble CD40 is absent in patients with unstable angina
Michitaka Tsuzuki1, Itsuro Morishima, Tomohiro Yoshida
1Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. mtsuzuki@med.nagoya-u.ac.jp
Insights
The balance between CD40 and CD40 ligand (CD40L) may be disrupted in unstable angina. Soluble CD40 levels correlate with matrix metalloproteinase-9, suggesting a role in atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Immunology
- Atherosclerosis Research
Background:
- The CD40/CD40 ligand (CD40L) system plays a role in inflammation and atherogenesis.
- Soluble CD40 (sCD40) can suppress CD40L expression in vitro.
- The relationship between soluble CD40L (sCD40L) and sCD40 in unstable angina (UA) is not well understood.
Purpose of the Study:
- To investigate the relationship between sCD40L and sCD40 in patients with unstable angina.
- To explore the association of sCD40 and sCD40L with matrix metalloproteinase (MMP)-9 levels in UA.
Main Methods:
- Enzyme-linked immunosorbent assays were used to measure serum levels of sCD40L and sCD40.
- Plasma levels of MMP-9 were also quantified.
- Patients with recent chest pain were categorized into UA (n=19) and control (n=18) groups based on coronary stenosis and clinical criteria.
Main Results:
- A significant inverse correlation between sCD40L and sCD40 was observed in controls (r = -0.72, P = 0.0007) but not in UA patients (r = -0.16, P > 0.05).
- The difference in regression slopes between UA and control groups was statistically significant (P < 0.01).
- A significant positive correlation was found between sCD40 and MMP-9 levels in all patients (r = 0.58, P = 0.0096), while sCD40L did not correlate with MMP-9.
Conclusions:
- The balance between CD40 and CD40L appears to be altered in patients with unstable angina.
- Soluble CD40 levels may be associated with MMP-9 expression, potentially contributing to atherosclerotic processes.
Abstract:
The CD40/CD40 ligand (CD40L) system mediates inflammatory processes important in atherogenesis and plaque instability. The expression of CD40L on activated T cells was suppressed by soluble CD40 (sCD40) in vitro. However, the relationship between soluble CD40L (sCD40L) and sCD40 in unstable angina (UA) is still unknown. Thirty-seven consecutive patients with recent chest pain or discomfort were recruited. Patients with both Braunwald's class IB-IIIB and with coronary stenosis (or stenoses) of >75% were assigned to the UA group (n = 19, aged 67.2 +/- 8.2 years), and the rest to the control group (n = 18, aged 63.4 +/- 8.7 years). The serum levels of sCD40L and sCD40, and the plasma levels of matrix metalloproteinase (MMP)-9, were measured by enzyme-linked immunosorbent assays. A significantly inverse correlation between sCD40L and sCD40 was shown in the controls (r = -0.72, P = 0.0007), but was absent in the UA group (r = -0.16, P not significant), although there was no statistical significance between these groups in terms of serum levels of sCD40L or sCD40. The difference of the regression slopes of these regression lines was statistically significant (P < 0.01). Additionally, there was a significant correlation between sCD40 and plasma levels of MMP-9 in the patients with and without UA (r = 0.58, P = 0.0096), but no significant correlation between sCD40L and MMP-9 levels (r = 0.00, P not significant). The balance between CD40 and CD40L may be lost in patients with UA. Soluble CD40 expression may also be related to MMP-9 expression in atherosclerotic tissues.