Cytokine Disturbances in Coronary Artery Ectasia Do Not Support Atherosclerosis Pathogenesis

Usama Boles, Anders Johansson, Urban Wiklund, Zain Sharif, Santhosh David, Siobhan McGrory, Michael Y Henein, Usama Boles, Anders Johansson, Urban Wiklund, Zain Sharif, Santhosh David, Siobhan McGrory, Michael Y Henein

Abstract

Background: Coronary artery ectasia (CAE) is a rare disorder commonly associated with additional features of atherosclerosis. In the present study, we aimed to examine the systemic immune-inflammatory response that might associate CAE.

Methods: Plasma samples were obtained from 16 patients with coronary artery ectasia (mean age 64.9 ± 7.3 years, 6 female), 69 patients with coronary artery disease (CAD) and angiographic evidence for atherosclerosis (age 64.5 ± 8.7 years, 41 female), and 140 controls (mean age 58.6 ± 4.1 years, 40 female) with normal coronary arteries. Samples were analyzed at Umeå University Biochemistry Laboratory, Sweden, using the V-PLEX Pro-Inflammatory Panel 1 (human) Kit. Statistically significant differences (p < 0.05) between patient groups and controls were determined using Mann-Whitney U-tests.

Results: The CAE patients had significantly higher plasma levels of INF-γ, TNF-α, IL-1β, and IL-8 (p = 0.007, 0.01, 0.001, and 0.002, respectively), and lower levels of IL-2 and IL-4 (p < 0.001 for both) compared to CAD patients and controls. The plasma levels of IL-10, IL-12p, and IL-13 were not different between the three groups. None of these markers could differentiate between patients with pure (n = 6) and mixed with minimal atherosclerosis (n = 10) CAE.

Conclusions: These results indicate an enhanced systemic pro-inflammatory response in CAE. The profile of this response indicates activation of macrophages through a pathway and trigger different from those of atherosclerosis immune inflammatory response.

Keywords: atherosclerosis; coronary artery disease; coronary artery ectasia; cytokines; immune inflammatory response; macrophage activation.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Cytokines with significantly higher levels in CAE patients compared to controls. P-values are derived from Kruskal–Wallis test of all three groups (see Table 2). CAE patients also presented with significantly higher levels IL-1β and IL-8 than CAD patients. Boxes show median and interquartile. Dashed lines indicate the threshold for defining extreme values, which are shown in a compressed region between the solid lines.
Figure 2
Figure 2
Systematic diagram to illustrate the enhanced pro inflammatory systemic response in CAE. Macrophage activation and the cytokines response. The proposed TH2 pathway activation leads to increased IL-6. However, low IL-4 levels as an outcome of possibly perturbed NK T-cell function lead to poor healing.

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