ST2L Transmembrane Receptor Expression: An Immunochemical Study on Endarterectomy Samples

Abstract

Background: ST2 (suppression of tumorigenity) has been described as a receptor for the interleukin-33, a member of the IL-1 family of cytokines. It is associated to coronary artery disease, all-causes mortality and cardiovascular mortality.

Aims: The present study was designed to assess the immunohistochemical expression of the ST2 receptor (ST2L/Il-1R) in atherosclerotic plaques of formalin fixed paraffin-embedded internal carotid arteries of patients with and without cerebro-vascular symptoms.

Methods and results: The study involved 41 cases (23 asymptomatic and 18 symptomatic). All the clinical and morphological parameters examined were uniformly distributed between the two groups, with a mild predominance of degree of calcification in asymptomatic cases (p = 0.01). ST2L expression was found to be more evident as a membrane pattern in macrophages when observing carotid atherosclerotic plaques of symptomatic patients, rather than in asymptomatic patients' plaques (77.7% vs 39.1%; p = 0.015), and its expression was particularly remarkable in VI type plaque (AHA). Significantly, ST2L was marked by the endothelium of neoangiogenetic vessels on the shoulder region of the plaque, but not (apart from a few cases) in the endothelium covering the residual lumen of the vessel.

Conclusions: The ST2L immunohistochemical expression was for the first time investigated in a large number of human carotid atherosclerotic plaques, as for its pattern of distribution in the different plaque cell populations. Furthermore, ST2L was particularly remarkable on macrophages, as a membrane pattern, of symptomatic patients' plaque. Considering our data, we hypothesize that ST2L/IL33 axis could drive the mechanism of plaque development and eventually rupture.

Fig 1. The graph illustrates the correlation between the histological classification (AHA^4-5) and the expression of macrophage membrane pattern.

The line chart witnessed an evident increasing of macrophage membrane pattern in VI class plaques. The histological classification of AHA defines VI class lesions as atheroma. Usually, type VI lesions episodes may quickly lead to occlusion and to be symptomatic for patients. It highlights our theories that the immunochemical ST2 membrane pattern has a direct correlation in terms of symptoms, and it could be a marker to detect vulnerable plaques.

Fig 2

a). ST2 immuno-reactivity in macrophages with an evident membrane pattern. Concomitant expression in endothelial cells of new formed capillaries. (ST2 immunoreaction; 200 X original magnification). 2b) ST2 immuno-expression with a membrane pattern was particularly evident in foreign body giant cells of atherosclerotic plaques (ST2 immunoreaction; 200 X original magnification). 2c). A lymphatic follicle showing diffuse expression of ST2; a contiguous small capillary presents an intense endothelial positivity (ST2 immunoreaction; 400 X original magnification). 2d) Strong immuno-reactivity on endothelial cells of a newly formed vessel (ST 2 immunoreaction; 400 X original magnification). 2e) A lymphatic follicle (the same lymphatic follicle of Fig 2c) with intense immunostaining for CD 20; 400 X original magnification).