17 beta-Oestradiol produced an endothelium independent relaxation of precontracted human coronary arteries in vitro, and this effect was associated with an increase in both cyclic AMP and the cyclic GMP content. This direct relaxant effect of oestrogens on coronary arteries may contribute to the beneficial effects of oestrogen replacement therapy in postmenopausal women.

Aims  Acute coronary syndromes with intact fibrous cap (IFC-ACS), i.e. caused by coronary plaque erosion, account for approximately one-third of ACS. However, the underlying pathophysiological mechanisms as compared with ACS caused by plaque rupture (RFC-ACS) remain largely undefined. The prospective translational OPTICO-ACS study programme investigates for the first time the microenvironment of ACS-causing culprit lesions (CL) with intact fibrous cap by molecular high-resolution intracoronary imaging and simultaneous local immunological phenotyping. Methods and results  The CL of 170 consecutive ACS patients were investigated by optical coherence tomography (OCT) and simultaneous immunophenotyping by flow cytometric analysis as well as by effector molecule concentration measurements across the culprit lesion gradient (ratio local/systemic levels). Within the study cohort, IFC caused 24.6% of ACS while RFC-ACS caused 75.4% as determined and validated by two independent OCT core laboratories. The IFC-CL were characterized by lower lipid content, less calcification, a thicker overlying fibrous cap, and largely localized near a coronary bifurcation as compared with RFC-CL. The microenvironment of IFC-ACS lesions demonstrated selective enrichment in both CD4+ and CD8+ T-lymphocytes (+8.1% and +11.2%, respectively, both P < 0.05) as compared with RFC-ACS lesions. T-cell-associated extracellular circulating microvesicles (MV) were more pronounced in IFC-ACS lesions and a significantly higher amount of CD8+ T-lymphocytes was detectable in thrombi aspirated from IFC-culprit sites. Furthermore, IFC-ACS lesions showed increased levels of the T-cell effector molecules granzyme A (+22.4%), perforin (+58.8%), and granulysin (+75.4%) as compared with RFC plaques (P < 0.005). Endothelial cells subjected to culture in disturbed laminar flow conditions, i.e. to simulate coronary flow near a bifurcation, demonstrated an enhanced adhesion of CD8+T cells. Finally, both CD8+T cells and their cytotoxic effector molecules caused endothelial cell death, a key potential pathophysiological mechanism in IFC-ACS. Conclusions  The OPTICO-ACS study emphasizes a novel mechanism in the pathogenesis of IFC-ACS, favouring participation of the adaptive immune system, particularly CD4+ and CD8+ T-cells and their effector molecules. The different immune signatures identified in this study advance the understanding of coronary plaque progression and may provide a basis for future development of personalized therapeutic approaches to ACS with IFC. Trial registration The study was registered at clinicalTrials.gov (NCT03129503).

Gangliocytomas are benign, slow growing neuronal tumors and are found for the most part in children and young adults. They are most often localized in either the spinal cord or the cerebral hemispheres. Gangliocytomas in the sellar region are extremely rare and only 43 such tumors (including 4 own cases) have ever been described in the literature. Although these tumors are genuine rarities without any epidemiological importance, they do provide some interesting information on tumorigenesis of pituitary adenomas: 65% of the sellar gangliocytomas are associated with a pituitary adenoma. 74% of patients with these tumors suffered hormonal oversecretion of at least one of the pituitary hormones (mostly growth hormone). With only one exception, the hypothalamic releasing hormone corresponding to the hormonal oversecretion syndrome could be demonstrated in the gangliocytoma immunohistochemically. Ultrastructural studies could demonstrate close cell to cell contacts between adenoma and gangliocytome cells. All these data support the hypothesis that chronic overstimulation by hypothalamic releasing hormones play a role in the development of hormone secreting pituitary adenomas. However, in contrast to sellar gangliocytemas, extrahypothalamic tumors secreting excessive hypothalamic hypophysiotropic hormones have never been associated with a pituitary adenoma. They have only been associated with pituitary cell hyperplasia. Therefore, the hypothesis can be made that hypothalamic releasing hormones only promote but do not initiate tumorigenesis of pituitary adenomas.

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